MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'DNA Repair' source. Mon, 06 Feb 2012 09:32:06 +0100 http://www.medworm.com/index.php?rid=5650998&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22284908%26dopt%3DAbstract CONCLUSIONS: The existence of a significant correlation between blood and tumour tissue expression of some genes of clinical interest, such as ERCC1 in NSCLC and HNSCC, could allow the introduction in clinical practice of a simple test that would measure mRNA levels of DNA repair genes in peripheral blood samples instead of tissue samples to determine prognostic and predictive factors in NSCLC and HNSCC patients. PMID: 22284908 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5650998 Wed, 25 Jan 2012 05:00:00 +0100 5650998 http://www.medworm.com/index.php?rid=5650999&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22281126%26dopt%3DAbstract Authors: Hanssen-Bauer A, Solvang-Garten K, Gilljam KM, Torseth K, Wilson DM, Akbari M, Otterlei M Abstract XRCC1 functions as a non-enzymatic, scaffold protein in single strand break repair (SSBR) and base excision repair (BER). Here, we examine different regions of XRCC1 for their contribution to the scaffolding functions of the protein. We found that the central BRCT1 domain is essential for recruitment of XRCC1 to sites of DNA damage and DNA replication. Also, we found that ectopic expression of the region from residue 166-436 partially rescued the methyl methanesulfonate (MMS) hypersensitivity of XRCC1-deficient EM9 cells, suggesting a key role for this region in mediating DNA repair. The three most common amino acid variants of XRCC1, Arg194Trp, Arg280His and Arg399Gln, are l... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5650999 Tue, 24 Jan 2012 05:00:00 +0100 5650999 http://www.medworm.com/index.php?rid=5636046&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22277748%26dopt%3DAbstract Authors: Covo S, Westmoreland JW, Reddy AK, Gordenin DA, Resnick MA Abstract The yeast Chk2/Chk1 homolog Rad53 is a central component of the DNA damage checkpoint system. While it controls genotoxic stress responses such as cell cycle arrest, replication fork stabilization and increase in dNTP pools, little is known about the consequences of reduced Rad53 levels on the various cellular endpoints or about its roles in dealing with chronic vs. acute genotoxic challenges. Using a tetraploid gene dosage model in which only one copy of the yeast RAD53 is functional (simplex), we found that the simplex strain was not sensitive to acute UV radiation or chronic MMS exposure. However, the simplex strain was sensitized to chronic exposure of the ribonucleotide reductase inhibitor hydroxyurea... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5636046 Mon, 23 Jan 2012 05:00:00 +0100 5636046 http://www.medworm.com/index.php?rid=5636047&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22265216%26dopt%3DAbstract Authors: Shao Z, Davis AJ, Fattah KR, So S, Sun J, Lee KJ, Harrison L, Yang J, Chen DJ Abstract DNA double strand breaks (DSBs) are repaired by non-homologous end joining (NHEJ) or homologous recombination (HR). The DNA cell cycle stage and resection of the DSB ends are two key mechanisms which are believed to push DSB repair to the HR pathway. Here, we show that the NHEJ factor Ku80 associates with DSBs in S phase, when HR is thought to be the preferred repair pathway, and its dynamics/kinetics at DSBs is similar to those observed for Ku80 in non-S phase in mammalian cells. A Ku homolog from Mycobacterium tuberculosis binds to and is retained at DSBs in S phase and was used as a tool to determine if blocking DNA ends affects end resection and HR in mammalian cells. A decrease in D... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5636047 Thu, 19 Jan 2012 05:00:00 +0100 5636047 http://www.medworm.com/index.php?rid=5594242&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22237014%26dopt%3DAbstract Authors: Roth HM, Römer J, Grundler V, Van Houten B, Kisker C, Tessmer I Abstract Bax1 has recently been identified as a novel binding partner for the archaeal helicase XPB. We previously characterized Bax1 from Thermoplasma acidophilum as a Mg(2+)-dependent structure-specific endonuclease. Here we directly compare the endonuclease activity of Bax1 alone or in combination with XPB. Using several biochemical and biophysical approaches, we demonstrate regulation of Bax1 endonuclease activity by XPB. Interestingly, incision assays with Bax1 and XPB/Bax1 clearly demonstrate that Bax1 produces different incision patterns depending on the presence or absence of XPB. Using atomic force microscopy (AFM), we directly visualize and compare binding of Bax1 and XPB/Bax1 to different DNA subst... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5594242 Mon, 09 Jan 2012 05:00:00 +0100 5594242 http://www.medworm.com/index.php?rid=5594249&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22230721%26dopt%3DAbstract CONCLUSION: Our study found that a promoter region SNP in the editing and processing nucleases gene EXO1 was associated with decreased expression of EXO1 and decreased melanoma risk. Further studies are warranted to validate this association and to investigate the potential mechanisms. PMID: 22230721 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5594249 Sat, 07 Jan 2012 05:00:00 +0100 5594249 http://www.medworm.com/index.php?rid=5594255&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226374%26dopt%3DAbstract Authors: Collura A, Auffret Van Der Kemp P, Boiteux S Abstract In Saccharomyces cerevisiae, inactivation of base excision repair (BER) AP endonucleases (Apn1p and Apn2p) results in constitutive phosphorylation of Rad53p and delay in cell cycle progression at the G2/M transition. These data led us to investigate genetic interactions between Apn1p, Apn2p and DNA damage checkpoint proteins. The results show that mec1 sml1, rad53 sml1 and rad9 is synthetic lethal with apn1 apn2. In contrast, apn1 apn2 rad17, apn1 apn2 ddc1 and apn1 apn2 rad24 triple mutants are viable, although they exhibit a strong Can(R) spontaneous mutator phenotype. In these strains, high Can(R) mutation rate is dependent upon functional uracil DNA N-glycosylase (Ung1p) and mutation spectra are dominated by AT to C... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5594255 Wed, 04 Jan 2012 05:00:00 +0100 5594255 http://www.medworm.com/index.php?rid=5594258&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22222486%26dopt%3DAbstract Authors: Andersen SD, Keijzers G, Rampakakis E, Engels K, Luhn P, El-Shemerly M, Nielsen FC, Du Y, May A, Bohr VA, Ferrari S, Zannis-Hadjopoulos M, Fu H, Rasmussen LJ Abstract Human exonuclease 1 (hEXO1) acts directly in diverse DNA processing events, including replication, mismatch repair (MMR), and double strand break repair (DSBR), and it was also recently described to function as damage sensor and apoptosis inducer following DNA damage. In contrast, 14-3-3 proteins are regulatory phosphorserine/threonine binding proteins involved in the control of diverse cellular events, including cell cycle checkpoint and apoptosis signaling. hEXO1 is regulated by post-translation Ser/Thr phosphorylation in a yet not fully clarified manner, but evidently three phosphorylation sites are specif... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5594258 Tue, 03 Jan 2012 05:00:00 +0100 5594258 http://www.medworm.com/index.php?rid=5594257&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226011%26dopt%3DAbstract Authors: PMID: 22226011 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5594257 Mon, 02 Jan 2012 05:00:00 +0100 5594257 http://www.medworm.com/index.php?rid=5594256&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22226012%26dopt%3DAbstract Authors: Friedberg EC PMID: 22226012 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5594256 Mon, 02 Jan 2012 05:00:00 +0100 5594256 http://www.medworm.com/index.php?rid=5574926&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209780%26dopt%3DAbstract Authors: Halsne R, Esbensen Y, Wang W, Scheffler K, Suganthan R, Bjørås M, Eide L Abstract Reactive oxygen species (ROS) are formed as natural byproducts during aerobic metabolism and readily induce premutagenic base lesions in the DNA. The 8-oxoguanine DNA glycosylase (OGG1) and MutY homolog 1 (MYH) synergistically prevent mutagenesis and cancer formation in mice. Their localization in the mitochondria as well as in the nucleus suggests that mutations in mitochondrial DNA (mtDNA) contribute to the carcinogenesis in the myh(-/-)/ogg1(-/-) double knockout mouse. In order to test this hypothesis, we analyzed mtDNA mutagenesis and mitochondrial function in young (1month) and adult (6months) wt and myh(-/-)/ogg1(-/-) mice. To our surprise, the absence of OGG1 and MYH had no impact on... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5574926 Fri, 30 Dec 2011 05:00:00 +0100 5574926 http://www.medworm.com/index.php?rid=5574927&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22209521%26dopt%3DAbstract We describe here the involvement of the AMPK-MAPO1-FLCN complex in the signaling pathway of apoptosis induced by O(6)-methylguanine. By the introduction of siRNAs specific for these genes, the transition of cells to a population with sub-G(1) DNA content following MNU treatment was significantly suppressed. After MNU exposure, phosphorylation of AMPKα occurred in an MLH1-dependent manner, and this activation of AMPK was not observed in cells in which the expression of either the Mapo1 or the Flcn gene was downregulated. When cells were treated with AICA-ribose (AICAR), a specific activator of AMPK, activation of AMPK was also observed in a MAPO1- and FLCN-dependent manner, thus leading to cell death which was accompanied by the depolarization of the mitochondrial membrane, a hallmark of t... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5574927 Thu, 29 Dec 2011 05:00:00 +0100 5574927 http://www.medworm.com/index.php?rid=5543676&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22188649%26dopt%3DAbstract Authors: Fujinaka Y, Matsuoka K, Iimori M, Tuul M, Sakasai R, Yoshinaga K, Saeki H, Morita M, Kakeji Y, Gillespie DA, Yamamoto KI, Takata M, Kitao H, Maehara Y Abstract 5-Fluorouracil (5-FU) has long been a mainstay antimetabolite chemotherapeutic drug for the treatment of major solid tumors, particularly colorectal cancer. 5-FU is processed intracellularly to yield active metabolites that compromise RNA and DNA metabolism. However, the mechanisms responsible for its cytotoxicity are not fully understood. From the phenotypic analysis of mutant chicken B lymphoma DT40 cells, we found that homologous recombinational repair (HRR), involving Rad54 and BRCA2, and the ATR-Chk1 signaling pathway, involving Rad9 and Rad17, significantly contribute to 5-FU tolerance. 5-FU induced γH2AX nuc... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5543676 Mon, 19 Dec 2011 05:00:00 +0100 5543676 http://www.medworm.com/index.php?rid=5543677&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22186232%26dopt%3DAbstract Authors: Kumari A, Lim YX, Newell AH, Olson SB, McCullough AK Abstract Formaldehyde is a reactive chemical that is commonly used in the production of industrial, laboratory, household, and cosmetic products. The causal association between formaldehyde exposure and increased incidence of cancer led the International Agency for Research on Cancer to classify formaldehyde as a carcinogen. Formaldehyde-induced DNA-protein crosslinks (DPCs) elicit responses involving nucleotide excision repair (NER) and homologous recombination (HR) repair pathways; however, little is known about the cellular and genetic changes that subsequently lead to formaldehyde-induced genotoxic and cytotoxic effects. Herein, investigations of genes that modulate the cytotoxic effects of formaldehyde exposure reve... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5543677 Sun, 18 Dec 2011 05:00:00 +0100 5543677 http://www.medworm.com/index.php?rid=5543675&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22191104%26dopt%3DAbstract Authors: Painter R PMID: 22191104 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5543675 Sat, 10 Dec 2011 05:00:00 +0100 5543675 http://www.medworm.com/index.php?rid=5409092&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22082992%26dopt%3DAbstract Authors: PMID: 22082992 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5409092 Wed, 16 Nov 2011 22:18:12 +0100 5409092 http://www.medworm.com/index.php?rid=5409093&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22079122%26dopt%3DAbstract Authors: Fu D, Samson LD Abstract Exocyclic ethenobases are highly mutagenic DNA lesions strongly implicated in inflammation and vinyl chloride-induced carcinogenesis. While the alkyladenine DNA glycosylase, AAG (or MPG), binds the etheno lesions 1,N(6)-ethenoadenine (ɛA) and 3,N(4)-ethenocytosine (ɛC) with high affinity, only ɛA can be excised to initiate base excision repair. Here, we discover that the human AlkB homolog 2 (ALKBH2) dioxygenase enzyme catalyzes direct reversal of ɛC lesions in both double- and single-stranded DNA with comparable efficiency to canonical ALKBH2 substrates. Notably, we find that in vitro, the non-enzymatic binding of AAG to ɛC specifically blocks ALKBH2-catalyzed repair of ɛC but not that of methylated ALKBH2 substrates. These results identify ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5409093 Thu, 10 Nov 2011 05:00:00 +0100 5409093 http://www.medworm.com/index.php?rid=5374661&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978436%26dopt%3DAbstract Authors: George CM, Lyndaker AM, Alani E Abstract In the early steps of homologous recombination, single-stranded DNA (ssDNA) from a broken chromosome invades homologous sequence located in a sister or homolog donor. In genomes that contain numerous repetitive DNA elements or gene paralogs, recombination can potentially occur between non-allelic/divergent (homeologous) sequences that share sequence identity. Such recombination events can lead to lethal chromosomal deletions or rearrangements. However, homeologous recombination events can be suppressed through rejection mechanisms that involve recognition of DNA mismatches in heteroduplex DNA by mismatch repair factors, followed by active unwinding of the heteroduplex DNA by helicases. Because factors required for heteroduplex rejec... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374661 Fri, 04 Nov 2011 16:56:51 +0100 5374661 http://www.medworm.com/index.php?rid=5374660&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21978437%26dopt%3DAbstract Authors: Yi YW, Bae I PMID: 21978437 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374660 Fri, 04 Nov 2011 16:56:42 +0100 5374660 http://www.medworm.com/index.php?rid=5374658&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22008257%26dopt%3DAbstract Authors: PMID: 22008257 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374658 Fri, 04 Nov 2011 16:56:25 +0100 5374658 http://www.medworm.com/index.php?rid=5374653&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22041023%26dopt%3DAbstract Authors: Zhang T, Huang J, Gu L, Li GM Abstract Expansion of CAG/CTG trinucleotide repeats (TNRs) in humans is associated with a number of neurological and neurodegenerative disorders including Huntington's disease. Increasing evidence suggests that formation of a stable DNA hairpin within CAG/CTG repeats during DNA metabolism leads to TNR instability. However, the molecular mechanism by which cells recognize and repair CAG/CTG hairpins is largely unknown. Recent studies have identified a novel DNA repair pathway specifically removing (CAG)(n)/(CTG)(n) hairpins, which is considered a major mechanism responsible for TNR instability. The hairpin repair (HPR) system targets the repeat tracts for incisions in the nicked strand in an error-free manner. To determine the substrate spectru... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374653 Sat, 29 Oct 2011 04:00:00 +0100 5374653 http://www.medworm.com/index.php?rid=5374652&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22041024%26dopt%3DAbstract Authors: Charret KS, Requena CE, Castillo-Acosta VM, Ruiz-Pérez LM, González-Pacanowska D, Vidal AE Abstract DNA repair mechanisms guarantee the maintenance of genome integrity, which is critical for cell viability and proliferation in all organisms. As part of the cellular defenses to DNA damage, apurinic/apyrimidinic (AP) endonucleases repair the abasic sites produced by spontaneous hydrolysis, oxidative or alkylation base damage and during base excision repair (BER). Trypanosoma brucei, the protozoan pathogen responsible of human sleeping sickness, has a class II AP endonuclease (TBAPE1) with a high degree of homology to human APE1 and bacterial exonuclease III. The purified recombinant enzyme cleaves AP sites and removes 3'-phosphoglycolate groups from 3'-ends. To study its c... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374652 Sat, 29 Oct 2011 04:00:00 +0100 5374652 http://www.medworm.com/index.php?rid=5374651&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22041025%26dopt%3DAbstract Authors: Mutamba JT, Svilar D, Prasongtanakij S, Wang XH, Lin YC, Dedon PC, Sobol RW, Engelward BP Abstract Inflammation associated reactive oxygen and nitrogen species (RONs), including peroxynitrite (ONOO(-)) and nitric oxide (NO), create base lesions that potentially play a role in the toxicity and large genomic rearrangements associated with many malignancies. Little is known about the role of base excision repair (BER) in removing these endogenous DNA lesions. Here, we explore the role of X-ray repair cross-complementing group 1 (XRCC1) in attenuating RONs-induced genotoxicity. XRCC1 is a scaffold protein critical for BER for which polymorphisms modulate the risk of cancer. We exploited CHO and human glioblastoma cell lines engineered to express varied levels of BER proteins t... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374651 Sat, 29 Oct 2011 04:00:00 +0100 5374651 http://www.medworm.com/index.php?rid=5374655&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036606%26dopt%3DAbstract In this study we generated mice with combined null alleles for Fanca and Fancg to identify extended functions for these genes by characterizing the double mutant mice and cells. Double mutant a(-/-)/g(-/-) mice were born at near Mendelian frequencies without apparent developmental abnormalities. Histological analysis of a(-/-)/g(-/-) mice revealed a Leydig cell hyperplasia and frequent vacuolization of Sertoli cells in testes, while ovaries were depleted from developing follicles and displayed an interstitial cell hyperplasia. These gonadal aberrations were associated with a compromised fertility of a(-/-)/g(-/-) males and females. During the first year of life a(-/-)/g(-/-) did not develop malignancies or bone marrow failure. At the cellular level a(-/-)/g(-/-), Fanca(-/-), and Fancg(-/-)... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374655 Fri, 28 Oct 2011 04:00:00 +0100 5374655 http://www.medworm.com/index.php?rid=5374654&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22036607%26dopt%3DAbstract In this study, we showed that RAD18 interacts with BRCTx in a phosphorylation-dependent manner and that this interaction, mediated via highly conserved serine residues on the RAD18 C terminus, is required for BRCTx accumulation at DNA damage sites. Furthermore, we uncovered critical roles of the RAD18-BRCTx module in UV-induced DNA damage repair but not PCNA mono-ubiquitination or homologous recombination. Thus, our results suggest that RAD18 has an additional function in the surveillance of the UV-induced DNA damage response signal. PMID: 22036607 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374654 Fri, 28 Oct 2011 04:00:00 +0100 5374654 http://www.medworm.com/index.php?rid=5374656&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024240%26dopt%3DAbstract Authors: Kim N, Mudrak SV, Jinks-Robertson S Abstract The bypass of AP sites in yeast requires the Rev1 protein in addition to the Pol ζ translesion synthesis DNA polymerase. Although Rev1 was originally characterized biochemically as a dCMP transferase during AP-site bypass, the relevance of this activity in vivo is unclear. The current study uses highly sensitive frameshift- and nonsense-reversion assays to monitor the bypass of AP sites created when uracil is excised from chromosomal DNA. In the frameshift-reversion assay, an unselected base substitution frequently accompanies the selected mutation, allowing the relative incorporation of each of the four dNMPs opposite endogenously created AP sites to be inferred. Results with this assay suggest that dCMP is the most frequent d... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374656 Sat, 22 Oct 2011 04:00:00 +0100 5374656 http://www.medworm.com/index.php?rid=5374657&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22018494%26dopt%3DAbstract Authors: Curtis MJ, Hays JB Abstract Conserved DNA-damage responses (DDRs) efficiently cope with replication blocks and double-strand breaks (DSBs) in cultured eukaryotic cells; DDRs in tissues remain poorly understood. DDR-inactivating mutations lethal in animals are tolerated in Arabidopsis, whose root meristem provides a powerful stem-cell-niche model. We imaged UVB-induced death of specific meristem cells in single and double Arabidopsis mutants to elucidate cooperation among DNA translesion synthesis (TLS) polymerases (Polη, Polζ) and DNA-damage-activated protein kinases (ATR, ATM). Death was 100-fold higher in stem and progenitor (StPr) cells than in transiently amplifying cells. Quantitative analyses of dose-response plots showed that Polη and Polζ act redundantly to tol... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374657 Fri, 21 Oct 2011 04:00:00 +0100 5374657 http://www.medworm.com/index.php?rid=5374659&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21993421%26dopt%3DAbstract Authors: Wiktor-Brown DM, Sukup-Jackson MR, Fakhraldeen SA, Hendricks CA, Engelward BP Abstract The tumor suppressor p53 is a transcription factor whose function is critical for maintaining genomic stability in mammalian cells. In response to DNA damage, p53 initiates a signaling cascade that results in cell cycle arrest, DNA repair or, if the damage is severe, programmed cell death. In addition, p53 interacts with repair proteins involved in homologous recombination. Mitotic homologous recombination (HR) plays an essential role in the repair of double-strand breaks (DSBs) and broken replication forks. Loss of function of either p53 or HR leads to an increased risk of cancer. Given the importance of both p53 and HR in maintaining genomic integrity, we analyzed the effect of p53 on ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5374659 Mon, 10 Oct 2011 04:00:00 +0100 5374659 http://www.medworm.com/index.php?rid=5293247&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21840268%26dopt%3DAbstract Authors: Madison DL, Stauffer D, Lundblad JR Abstract Poly(ADP)-ribose polymerase (PARP) inhibitors modify the enzymatic activity of PARP1/2. When certain PARP inhibitors are used either alone or in combination with DNA damage agents they may cause a G2/M mitotic arrest and/or apoptosis in a susceptible genetic context. PARP1 interacts with the cell cycle checkpoint proteins Ataxia Telangectasia Mutated (ATM) and ATM and Rad3-related (ATR) and therefore may influence growth arrest cascades. The PARP inhibitor PJ34 causes a mitotic arrest by an unknown mechanism in certain cell lines, therefore we asked whether PJ34 conditionally activated the checkpoint pathways and which downstream targets were necessary for mitotic arrest. We found that PJ34 produced a concentration dependent G2/... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293247 Fri, 07 Oct 2011 14:12:52 +0100 5293247 http://www.medworm.com/index.php?rid=5293246&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862420%26dopt%3DAbstract This is the response to the Letter to the Editor by Bakkenist et al. regarding article "CGK733 does not inhibit ATM or ATR kinase in H460 human lung cancer cells". DNA Repair (Amst). 2011 Oct 10;10(10):1002 Authors: Kim TK PMID: 21862420 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293246 Fri, 07 Oct 2011 14:12:44 +0100 5293246 http://www.medworm.com/index.php?rid=5293245&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880555%26dopt%3DAbstract Authors: Zheng XF, Prakash R, Saro D, Longerich S, Niu H, Sung P Abstract The budding yeast Mph1 protein, the putative ortholog of human FANCM, possesses a 3' to 5' DNA helicase activity and is capable of disrupting the D-loop structure to suppress chromosome arm crossovers in mitotic homologous recombination. Similar to FANCM, genetic studies have implicated Mph1 in DNA replication fork repair. Consistent with this genetic finding, we show here that Mph1 is able to mediate replication fork reversal, and to process the Holliday junction via DNA branch migration. Moreover, Mph1 unwinds 3' and 5' DNA Flap structures that bear key features of the D-loop. These biochemical results not only provide validation for a role of Mph1 in the repair of damaged replication forks, but they also o... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293245 Fri, 07 Oct 2011 14:12:17 +0100 5293245 http://www.medworm.com/index.php?rid=5293244&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21880556%26dopt%3DAbstract Authors: Ricceri F, Porcedda P, Allione A, Turinetto V, Polidoro S, Guarrera S, Rosa F, Voglino F, Pezzotti A, Minieri V, Accomasso L, Rocchietti EC, Orlando L, Giachino C, Matullo G Abstract DNA double-strand breaks (DSB) are the most lethal form of ionizing radiation-induced DNA damage, and failure to repair them results in cell death. In order to see if any associations exist between DNA repair gene polymorphisms and phenotypic profiles of DSB repair (DSBR) we performed a genotype-phenotype correlation study in 118 young healthy subjects (mean age 25.8±6.7years). Subjects were genotyped for 768 single nucleotide polymorphisms (SNPs) with a custom Illumina Golden Gate Assay, and an H2AX histone phosphorylation assay was done to test DSBR capacity. We found that H2AX phosphorylat... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293244 Fri, 07 Oct 2011 14:12:08 +0100 5293244 http://www.medworm.com/index.php?rid=5293243&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889425%26dopt%3DAbstract Authors: Huefner ND, Mizuno Y, Weil CF, Korf I, Britt AB Abstract The transposases of DNA transposable elements catalyze the excision of the element from the host genome, but are not involved in the repair of the resulting double-strand break. To elucidate the role of various host DNA repair and damage response proteins in the repair of the hairpin-ended double strand breaks (DSBs) generated during excision of the maize Ac element in Arabidopsis thaliana, we deep-sequenced hundreds of thousands of somatic excision products from a variety of repair- or response-defective mutants. We find that each of these repair/response defects negatively affects the preservation of the ends, resulting in an enhanced frequency of deletions, insertions, and inversions at the excision site. The spec... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293243 Fri, 07 Oct 2011 14:11:59 +0100 5293243 http://www.medworm.com/index.php?rid=5293242&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889915%26dopt%3DAbstract Authors: Ryabinina OP, Minko IG, Lasarev MR, McCullough AK, Lloyd RS Abstract The repair of cis-syn cyclobutane pyrimidine dimers (CPDs) can be initiated via the base excision repair (BER) pathway, utilizing pyrimidine dimer-specific DNA glycosylase/lyase enzymes (pdgs). However, prior to incision at lesion sites, these enzymes bind to non-damaged DNAs through charge-charge interactions. Following initial binding to DNA containing multiple lesions, the enzyme incises at most of these sites prior to dissociation. If a subset of these lesions are in close proximity, clustered breaks may be produced that could lead to decreased cell viability or increased mutagenesis. Based on the co-crystal structures of bacteriophage T4-pdg and homology modeling of a related enzyme from Paramecium b... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293242 Fri, 07 Oct 2011 14:11:50 +0100 5293242 http://www.medworm.com/index.php?rid=5293241&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21889916%26dopt%3DAbstract Authors: Krijger PH, van den Berk PC, Wit N, Langerak P, Jansen JG, Reynaud CA, de Wind N, Jacobs H Abstract The generation of high affinity antibodies in B cells critically depends on translesion synthesis (TLS) polymerases that introduce mutations into immunoglobulin genes during somatic hypermutation (SHM). The majority of mutations at A/T base pairs during SHM require ubiquitination of PCNA at lysine 164 (PCNA-Ub), which activates TLS polymerases. By comparing the mutation spectra in B cells of WT, TLS polymerase η (Polη)-deficient, PCNA(K164R)-mutant, and PCNA(K164R);Polη double-mutant mice, we now find that most PCNA-Ub-independent A/T mutagenesis during SHM is mediated by Polη. In addition, upon exposure to various DNA damaging agents, PCNA(K164R) mutant cells display st... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293241 Fri, 07 Oct 2011 14:11:42 +0100 5293241 http://www.medworm.com/index.php?rid=5293240&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21893433%26dopt%3DAbstract Authors: Wyman C, Lebbink J, Kanaar R Abstract Recently published crystal structures of different Mre11 and Rad50 complexes show the arrangement of these proteins and imply dramatic ligand-induced rearrangements with important functional consequences. PMID: 21893433 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293240 Fri, 07 Oct 2011 14:11:32 +0100 5293240 http://www.medworm.com/index.php?rid=5293239&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21962831%26dopt%3DAbstract Authors: PMID: 21962831 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293239 Fri, 07 Oct 2011 14:11:13 +0100 5293239 http://www.medworm.com/index.php?rid=5293234&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975119%26dopt%3DAbstract Authors: Pryor JM, Washington MT Abstract Rev1 is a eukaryotic DNA polymerase that rescues replication forks stalled at sites of DNA damage by inserting nucleotides opposite the damaged template bases. Yeast genetic studies suggest that Rev1 plays an important role in rescuing replication forks stalled at one of the most common forms of DNA damage, an abasic site; however, steady state kinetic studies suggest that an abasic site acts as a significant block to nucleotide incorporation by Rev1. Here we examined the pre-steady state kinetics of nucleotide incorporation by yeast Rev1 with damaged and non-damaged DNA substrates. We found that yeast Rev1 is capable of rapid nucleotide incorporation, but only a small fraction of the protein molecules possessed this robust activity. We cha... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293234 Mon, 03 Oct 2011 04:00:00 +0100 5293234 http://www.medworm.com/index.php?rid=5293233&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975120%26dopt%3DAbstract Authors: Huang M, Kennedy R, Ali AM, Moreau LA, Meetei AR, D'Andrea AD, Chen CC Abstract The Fanconi Anemia (FA) pathway encodes a DNA damage response activated by DNA damage-stalled replication forks. Current evidence suggests that the FA pathway initiates with DNA damage recognition by the FANCM complex (FANCM/FAAP24/MHF). However, genetic inactivation of FANCM in mouse and DT40 cells causes only a partial defect in the FA pathway activation, suggesting the existence of redundant DNA damage sensors. Here we show that the MutS homologs function in this capacity. A RNAi screen revealed that MSH2 silencing caused defective FA pathway activation, as assessed by damage-induced FANCD2 mono-ubiquitination. A similar FA pathway defect was observed with MSH3 or MSH6 silencing. MSH2 deplet... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293233 Mon, 03 Oct 2011 04:00:00 +0100 5293233 http://www.medworm.com/index.php?rid=5293238&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21963404%26dopt%3DAbstract Authors: Kelley MR PMID: 21963404 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293238 Sat, 01 Oct 2011 04:00:00 +0100 5293238 http://www.medworm.com/index.php?rid=5293237&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21968057%26dopt%3DAbstract Authors: Bouthier de la Tour C, Boisnard S, Norais C, Toueille M, Bentchikou E, Vannier F, Cox MM, Sommer S, Servant P Abstract The Deinococcus radiodurans bacterium exhibits an extreme resistance to ionizing radiation. Here, we investigated the in vivo role of DdrB, a radiation-induced Deinococcus specific protein that was previously shown to exhibit some in vitro properties akin to those of SSB protein from Escherichia coli but also to promote annealing of single stranded DNA. First we report that the deletion of the C-terminal motif of the DdrB protein, which is similar to the SSB C-terminal motif involved in recruitment to DNA of repair proteins, did neither affect cell radioresistance nor DNA binding properties of purified DdrB protein. We show that, in spite of their differen... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293237 Sat, 01 Oct 2011 04:00:00 +0100 5293237 http://www.medworm.com/index.php?rid=5293236&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21968058%26dopt%3DAbstract Authors: Chung G, O'Neil NJ, Rose AM Abstract A family of helicases that are important in maintaining genome stability is the iron-sulfur group. Members of this family include DOG-1/FANCJ, RTEL1, XPD and Chl1p/DDX11. In Caenorhabitis elegans, the predicted gene M03C11.2 has orthology to the CHL1 (Chromosome loss 1) gene in Saccharomyces cerevisiae and DDX11 (DEAD/H box polypeptide 11) in humans. In this paper, we show that the chl-1 gene in C. elegans is required for normal development and fertility. Mutants have lineage-independent cell proliferation defects that result in a Stu (sterile uncoordinated) phenotype, characterized by gonadal abnormalities and a reduced number of D motor neurons and seam cells. A chromosome stability defect is present in the germ cells, where an abnorm... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293236 Sat, 01 Oct 2011 04:00:00 +0100 5293236 http://www.medworm.com/index.php?rid=5293235&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21968059%26dopt%3DAbstract Authors: Silver HR, Nissley JA, Reed SH, Hou YM, Johnson ES Abstract The two Siz/PIAS SUMO E3 ligases Siz1 and Siz2 are responsible for the vast majority of sumoylation in Saccharomyces cerevisiae. We found that siz1Δ siz2Δ mutants are sensitive to ultra-violet (UV) light. Epistasis analysis showed that the SIZ genes act in the nucleotide excision repair (NER) pathway, and suggested that they participate both in global genome repair (GGR) and in the Rpb9-dependent subpathway of transcription-coupled repair (TCR), but have minimal role in Rad26-dependent TCR. Quantitative analysis of NER at the single-nucleotide level showed that siz1Δ siz2Δ is deficient in repair of both the transcribed and non-transcribed strands of the DNA. These experiments confirmed that the SIZ genes parti... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5293235 Sat, 01 Oct 2011 04:00:00 +0100 5293235 http://www.medworm.com/index.php?rid=5272332&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945626%26dopt%3DAbstract Authors: Liu Y, Kadyrov FA, Modrich P Abstract End-directed mismatch-provoked excision has been reconstituted in several purified systems. While 3'-directed excision displays a mismatch dependence similar to that observed in nuclear extracts (≈20-fold), the mismatch dependence of 5'-directed excision is only 3-4-fold, significantly less than that in extracts (8-10-fold). Utilizing a fractionation-based approach, we have isolated a single polypeptide that enhances mismatch dependence of reconstituted 5'-directed excision and have shown it to be identical to poly[ADP-ribose] polymerase 1 (PARP-1). Titration of reconstituted excision reactions or PARP-1-depleted HeLa nuclear extract with purified PARP-1 showed that the protein specifically enhances mismatch dependence of 5'-directed... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5272332 Fri, 23 Sep 2011 04:00:00 +0100 5272332 http://www.medworm.com/index.php?rid=5272334&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945094%26dopt%3DAbstract Authors: Reynolds GE, Gao Q, Miller D, Snow BE, Harrington LA, Murnane JP Abstract Telomerase serves to maintain telomeric repeat sequences at the ends of chromosomes. However, telomerase can also add telomeric repeat sequences at DNA double-strand breaks (DSBs), a process called chromosome healing. Here, we employed a method of inducing DSBs near telomeres to query the role of two proteins, PIF1 and NBS1, in chromosome healing in mammalian cells. PIF1 was investigated because the PIF1 homolog in Saccharomyces cerevisiae inhibits chromosome healing, as shown by a 1000-fold increase in chromosome in PIF1-deficient cells. NBS1 was investigated because the functional homolog of NBS1 in S. cerevisiae, Xrs2, is part of the Mre11/Rad50/Xrs2 complex that is required for chromosome healing... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5272334 Thu, 22 Sep 2011 04:00:00 +0100 5272334 http://www.medworm.com/index.php?rid=5272333&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21945095%26dopt%3DAbstract Authors: Taylor M, Moore K, Murray J, Aves SJ, Price C Abstract Initiation of DNA replication in eukaryotes is a highly conserved and ordered process involving the co-ordinated, stepwise association of distinct proteins at multiple origins of replication throughout the genome. Here, taking Schizosaccharomyces pombe as a model, the role of Rad4(TopBP1) in the assembly of the replication complex has been examined. Quantitative chromatin immunoprecipitation experiments confirm that Rad4(TopBP1) associates with origins of DNA replication and, in addition, demonstrate that the protein is not present within the active replisome. A direct interaction between Rad4(TopBP1) and Mcm10 is shown and this is reflected in the Rad4(TopBP1)-dependent origin association of Mcm10. Rad4(TopBP1) is als... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5272333 Thu, 22 Sep 2011 04:00:00 +0100 5272333 http://www.medworm.com/index.php?rid=5272335&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21944569%26dopt%3DAbstract Authors: Burmeister T, Gröger D, Kühn A, Hoelzer D, Thiel E, Reinhardt R Abstract The chromosomal translocation t(9;22)(q34;q22), with expression of the BCR-ABL1 fusion gene is the cytogenetic and molecular hallmark of chronic myeloid leukemia (CML) and a subset of acute lymphoblastic leukemia (ALL). Basically two types of BCR-ABL1 chimeric mRNA transcripts have been observed: (1) e13a2/e14a2 transcripts in CML and ALL, resulting from chromosomal breaks in the major breakpoint cluster region (M-bcr) of the BCR gene and (2) e1a2 transcripts in ALL resulting from breaks in the minor breakpoint cluster region (m-bcr) of the BCR gene. To gain a better understanding of this molecular alteration, we developed a long-distance inverse PCR (LDI PCR) method for M-bcr breakpoint identificat... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5272335 Wed, 21 Sep 2011 04:00:00 +0100 5272335 http://www.medworm.com/index.php?rid=5256282&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21940221%26dopt%3DAbstract Authors: Yang H, Yung M, Sikavi C, Miller JH Abstract DNA mismatch repair (MMR) systems can be classified as either MutH-dependent or MutH-independent. In bacteria, extensive studies have been conducted with the MutH-dependent MMR in Escherichia coli and its close relatives. The picture of MutH-independent MMR in other bacteria is less clear, as MMR components other than MutS and MutL have not been identified in the majority of bacteria. Bacillus anthracis is one of the MutH-less Gram(+) bacteria in the phylum of Firmicutes. We used papillation as a tool to search for B. anthracis new mutator strains and identified a spontaneous mutator that carries a minitransposon insertion in the BAS4289 locus. The mutational frequency and specificity exhibited in this mutant were comparable to ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5256282 Tue, 20 Sep 2011 04:00:00 +0100 5256282 http://www.medworm.com/index.php?rid=5256283&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21924963%26dopt%3DAbstract Authors: Kirkali G, Keles D, Canda AE, Terzi C, Reddy PT, Jaruga P, Dizdaroglu M, Oktay G Abstract Carcinogenesis may involve overproduction of oxygen-derived species including free radicals, which are capable of damaging DNA and other biomolecules in vivo. Increased DNA damage contributes to genetic instability and promote the development of malignancy. We hypothesized that the repair of oxidatively induced DNA base damage may be modulated in colorectal malignant tumors, resulting in lower levels of DNA base lesions than in surrounding pathologically normal tissues. To test this hypothesis, we investigated oxidatively induced DNA damage in cancerous tissues and their surrounding normal tissues of patients with colorectal cancer. The levels of oxidatively induced DNA lesions such a... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5256283 Thu, 15 Sep 2011 04:00:00 +0100 5256283 http://www.medworm.com/index.php?rid=5214624&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21900052%26dopt%3DAbstract Authors: Costanzo V Abstract Homologous recombination (HR) is required for faithful repair of double strand breaks (DSBs) and is believed to be important for DNA replication under stressful conditions in unicellular organisms. However, its role during DNA replication in high eukaryotes has always been elusive. In particular, due to the essential nature of its main players it has been difficult to dissect the direct role of HR in DNA replication. Recent studies revealed that some key HR factors such as Rad51 and BRCA2 play unexpected functions during DNA replication by protecting nascent DNA from Mre11 mediated degradation, which takes place at stalled replication forks. These novel functions appear to be essential to ensure smooth progression of DNA replication and to promote maint... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5214624 Mon, 05 Sep 2011 04:00:00 +0100 5214624 http://www.medworm.com/index.php?rid=5170197&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21864795%26dopt%3DAbstract Authors: PMID: 21864795 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5170197 Mon, 29 Aug 2011 09:40:17 +0100 5170197 http://www.medworm.com/index.php?rid=5170195&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21868291%26dopt%3DAbstract Authors: Noon AT, Goodarzi AA Abstract 53BP1 is an established player in the cellular response to DNA damage and is a canonical component of ionizing-radiation induced foci - that cadre of proteins which assemble at DNA double strand breaks following radiation exposure and which are readily visualized by immunofluorescence microscopy. While its roles in p53 regulation and cell cycle checkpoint activation have been studied for some time, the impact of 53BP1 on DNA double strand break rejoining has only come to light in the past few years. Convincing evidence now exists for 53BP1 significantly affecting the outcome of DNA double strand break repair in several contexts, many of which hint to an important role in modulating chromatin structure surrounding the break site. Here, we highl... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5170195 Mon, 22 Aug 2011 23:00:00 +0100 5170195 http://www.medworm.com/index.php?rid=5170196&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21865098%26dopt%3DAbstract Authors: Choi S, Toledo LI, Fernandez-Capetillo O, Bakkenist CJ PMID: 21865098 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5170196 Sun, 21 Aug 2011 23:00:00 +0100 5170196 http://www.medworm.com/index.php?rid=5170198&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21862420%26dopt%3DAbstract This is the response to the Letter to the Editor by Bakkenist et al. regarding article "CGK733 does not inhibit ATM or ATR kinase in H460 human lung cancer cells" DNA Repair (Amst). 2011 Aug 19; Authors: Kim TK PMID: 21862420 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5170198 Thu, 18 Aug 2011 23:00:00 +0100 5170198 http://www.medworm.com/index.php?rid=5086973&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798465%26dopt%3DAbstract Authors: PMID: 21798465 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5086973 Tue, 02 Aug 2011 19:02:11 +0100 5086973 http://www.medworm.com/index.php?rid=5086937&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21798466%26dopt%3DAbstract Authors: Friedberg EC PMID: 21798466 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=5086937 Tue, 02 Aug 2011 17:59:50 +0100 5086937 http://www.medworm.com/index.php?rid=5087001&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21788159%26dopt%3DAbstract Authors: Rippa V, Duilio A, di Pasquale P, Amoresano A, Landini P, Volkert MR aidB is one of the four genes of E. coli that is induced by alkylating agents and regulated by Ada protein. Three genes (ada, alkA, and alkB) encode DNA repair proteins that remove or repair alkylated bases. However, the role of AidB remains unclear despite extensive efforts to determine its function in cells exposed to alkylating agents. The E. coli AidB protein was identified as a component of the protein complex that assembles at strong promoters. We demonstrate that AidB protein preferentially binds to UP elements, AT rich transcription enhancer sequences found upstream of many highly expressed genes, several DNA repair genes, and housekeeping genes. AidB allows efficient transcription from promoters cont... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5087001 Fri, 22 Jul 2011 23:00:00 +0100 5087001 http://www.medworm.com/index.php?rid=5037361&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21757407%26dopt%3DAbstract Authors: Jin R, Sun Y, Qi X, Zhang H, Zhang Y, Li N, Ding W, Chen D The X-ray repair cross complementing group 1 (XRCC1) protein is involved in DNA base excision repair and its expression varies during the cell cycle. Although studies have demonstrated that rapid XRCC1-dependent single-strand break repair (SSBR) takes place specifically during S/G(2) phases, it remains unclear how it is regulated during the cell cycle. We found that XRCC1 is a direct regulatory target of E2F1 and further investigated the role of XRCC1 in DNA repair during the cell cycle. Saos2 primary osteosarcoma cells stably transfected with inducible E2F1-wt or mutant E2F1-132E were treated with hydroxurea (HU) for 36h and were subsequently withdrawn HU for 2-24h to test whether cell-cycle-dependent DNA SSBR require... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037361 Mon, 11 Jul 2011 23:00:00 +0100 5037361 http://www.medworm.com/index.php?rid=5037362&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21752727%26dopt%3DAbstract Authors: de Groote FH, Jansen JG, Masuda Y, Shah DM, Kamiya K, de Wind N, Siegal G Rev1 is a eukaryotic DNA polymerase of the Y family involved in translesion synthesis (TLS), a major damage tolerance pathway that allows DNA replication at damaged templates. Uniquely amongst the Y family polymerases, the N-terminal part of Rev1, dubbed the BRCA1 C-terminal homology (BRCT) region, includes a BRCT domain. While most BRCT domains mediate protein-protein interactions, Rev1 contains a predicted α-helix N-terminal to the BRCT domain and in human Replication Factor C (RFC) such a BRCT region endows the protein with DNA binding capacity. Here, we studied the DNA binding properties of yeast and mouse Rev1. Our results show that the BRCT region of Rev1 specifically binds to a 5' phosphorylated,... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037362 Sun, 10 Jul 2011 23:00:00 +0100 5037362 http://www.medworm.com/index.php?rid=5037363&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741887%26dopt%3DAbstract Authors: Vasko MR, Guo C, Thompson EL, Kelley MR Although exposure to ionizing radiation (IR) can produce significant neurotoxicity, the mechanisms mediating this toxicity remain to be determined. Previous studies using neurons isolated from the central nervous system show that IR produces reactive oxygen species and oxidative DNA damage in those cells. Because the base excision DNA repair pathway repairs single-base modifications caused by ROS, we asked whether manipulating this pathway by altering APE1 expression would affect radiation-induced neurotoxicity. In cultures of adult hippocampal and sensory neurons, IR produces DNA damage as measured by phosphorylation of histone H2A.X and results in dose-dependent cell death. In isolated sensory neurons, we demonstrate for the first time... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037363 Wed, 06 Jul 2011 23:00:00 +0100 5037363 http://www.medworm.com/index.php?rid=5037364&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21741328%26dopt%3DAbstract We report here comparisons of relative NER efficiencies with a set of stereoisomeric DNA lesions derived from metabolites of benzo[a]pyrene and equine estrogens in different sequence contexts, utilizing 21 samples. We found a general qualitative trend toward similar relative NER incision efficiencies for ∼65% of these substrates; the other cases deviate mostly by ∼30% or less from a perfect correlation, although several more distant outliers are also evident. This resemblance is consistent with the hypothesis that lesion recognition through β-hairpin insertion, a common feature of the two systems, is facilitated by local thermodynamic destabilization induced by the lesions in both cases. In the case of the UvrABC system, varying the nature of the UvrC endonuclease, while maintaining t... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037364 Tue, 05 Jul 2011 23:00:00 +0100 5037364 http://www.medworm.com/index.php?rid=5037366&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21727035%26dopt%3DAbstract In this study, the mutagenicity of the bay region diolepoxides (+)-anti-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (BPDE) and (±)-anti-1,2-dihydroxy-3,4-epoxy-1,2,3,4-tetrahydrodibenzo[a,h]anthracene (DBADE) and the fjord region diolepoxides (±)-anti-11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo[a,l]-pyrene (DBPDE) and (±)-anti-3,4-dihydroxy-1,2-epoxy-1,2,3,4-tetrahydrobenzo[c]-phenanthrene (BPhDE) was compared in nucleotide excision repair (NER) proficient and deficient hamster cell lines. The (32)P-postlabelling assay was applied to analyze DNA adduct levels and the Hprt gene mutation assay for monitoring mutations. Previously, we found that the mutagenicity per adduct was four times higher for DBPDE compared to BPDE in NER proficient cells. In these same c... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037366 Fri, 01 Jul 2011 23:00:00 +0100 5037366 http://www.medworm.com/index.php?rid=5037365&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21727036%26dopt%3DAbstract We reported previously that the hairpin adopted by TNR repeats contains a hot spot for oxidation. This finding prompted us to examine the possibility that the generation of a hairpin during a BER event exacerbates the toxic oxidation cycle due to accumulation of damage. Therefore, in this work we used mixed-sequence and TNR substrates containing a site-specific 8-oxoG lesion to define the kinetic parameters of human OGG1 (hOGG1) activity on duplex and hairpin substrates. We report that hOGG1 activity on TNR duplexes is indistinguishable from a mixed-sequence control. Thus, BER is initiated on TNR sequences as readily as non-repetitive DNA in order to start the toxic oxidation cycle. However, we find that for hairpin substrates hOGG1 has reduced affinity and excises 8-oxoG at a significantl... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037365 Fri, 01 Jul 2011 23:00:00 +0100 5037365 http://www.medworm.com/index.php?rid=5037367&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21723207%26dopt%3DAbstract Authors: Brem R, Daehn I, Karran P Patients taking the immunosuppressant and anticancer thiopurines 6-mercaptopurine, azathioprine or 6-thioguanine (6-TG), develop skin cancer at a very high frequency. Their DNA contains 6-TG which absorbs ultraviolet A (UVA) radiation, and their skin is UVA hypersensitive, consistent with the formation of DNA photodamage. Here we demonstrate that UVA irradiation of 6-TG-containing DNA causes DNA interstrand crosslinking. In synthetic duplex oligodeoxynucleotides, the interstrand crosslinks (ICLs) can form between closely opposed 6-TG bases and, in a less favoured reaction, between 6-TG and normal bases on the opposite strand. In vivo, UVA irradiation of cultured cells containing 6-TG-substituted DNA also causes ICL formation and induces the chromosome... DNA Repair journals http://www.medworm.com/rss/comments.php?id=5037367 Tue, 28 Jun 2011 23:00:00 +0100 5037367 http://www.medworm.com/index.php?rid=4993649&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21703943%26dopt%3DAbstract Authors: Watt DL, Johansson E, Burgers PM, Kunkel TA The major replicative DNA polymerases of S. cerevisiae (Pols α, δ, and ɛ) incorporate substantial numbers of ribonucleotides into DNA during DNA synthesis. When these ribonucleotides are not removed in vivo, they reside in the template strand used for the next round of replication and could potentially reduce replication efficiency and fidelity. To examine if the presence of ribonucleotides in a DNA template impede DNA synthesis, we determined the efficiency with which Pols α, δ, and ɛ copy DNA templates containing a single ribonucleotide. All three polymerases can replicate past ribonucleotides. Relative to all-DNA templates, bypass of ribo-containing templates is slightly reduced, to extents that depend on the identity of the... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4993649 Tue, 21 Jun 2011 23:00:00 +0100 4993649 http://www.medworm.com/index.php?rid=4993650&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21684221%26dopt%3DAbstract Authors: Naegeli H, Sugasawa K The nucleotide excision repair (NER) system is a fundamental cellular stress response that uses only a handful of DNA binding factors, mutated in the cancer-prone syndrome xeroderma pigmentosum (XP), to detect an astounding diversity of bulky base lesions, including those induced by ultraviolet light, electrophilic chemicals, oxygen radicals and further genetic insults. Several of these XP proteins are characterized by a mediocre preference for damaged substrates over the native double helix but, intriguingly, none of them recognizes injured bases with sufficient selectivity to account for the very high precision of bulky lesion excision. Instead, substrate versatility as well as damage specificity and strand selectivity are achieved by a multistage quali... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4993650 Wed, 15 Jun 2011 23:00:00 +0100 4993650 http://www.medworm.com/index.php?rid=4894194&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21622030%26dopt%3DAbstract This study provides the first evidence that interactions involving MDC1 can be regulated by ubiquitylation. PMID: 21622030 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894194 Thu, 26 May 2011 23:00:00 +0100 4894194 http://www.medworm.com/index.php?rid=4894193&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21622031%26dopt%3DAbstract Authors: Lagerwerf S, Vrouwe MG, Overmeer RM, Fousteri MI, Mullenders LH A network of DNA damage surveillance systems is triggered by sensing of DNA lesions and the initiation of a signal transduction cascade that activates genome-protection pathways including nucleotide excision repair (NER). NER operates through coordinated assembly of repair factors into pre- and post-incision complexes. Recent work identifies RPA as a key regulator of the transition from dual incision to repair-synthesis in UV-irradiated non-cycling cells, thereby averting the generation of unprocessed repair intermediates. These intermediates could lead to recombinogenic events and trigger a persistent ATR-dependent checkpoint signaling. It is now evident that DNA damage signaling is not limited to NER proficient ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894193 Thu, 26 May 2011 23:00:00 +0100 4894193 http://www.medworm.com/index.php?rid=4894192&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21622032%26dopt%3DAbstract Authors: Stone JE, Kumar D, Binz SK, Inase A, Iwai S, Chabes A, Burgers PM, Kunkel TA DNA polymerase zeta (Pol ζ) participates in translesion synthesis (TLS) of DNA adducts that stall replication fork progression. Previous studies have led to the suggestion that the primary role of Pol ζ in TLS is to extend primers created when another DNA polymerase inserts nucleotides opposite lesions. Here we test the non-exclusive possibility that Pol ζ can sometimes perform TLS in the absence of any other polymerase. To do so, we quantified the efficiency with which S. cerevisiae Pol ζ bypasses abasic sites, cis-syn cyclobutane pyrimidine dimers and (6-4) photoproducts. In reactions containing dNTP concentrations that mimic those induced by DNA damage, a Pol ζ derivative with phenylalanine su... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894192 Thu, 26 May 2011 23:00:00 +0100 4894192 http://www.medworm.com/index.php?rid=4894195&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21612988%26dopt%3DAbstract Authors: Gregg SQ, Robinson AR, Niedernhofer LJ ERCC1-XPF is a structure-specific endonuclease required for nucleotide excision repair, interstrand crosslink repair, and the repair of some double-strand breaks. Mutations in ERCC1 or XPF cause xeroderma pigmentosum, XFE progeroid syndrome or cerebro-oculo-facio-skeletal syndrome, characterized by increased risk of cancer, accelerated aging and severe developmental abnormalities, respectively. This review provides a comprehensive overview of the health impact of ERCC1-XPF deficiency, based on these rare diseases and mouse models of them. This offers an understanding of the tremendous health impact of DNA damage derived from environmental and endogenous sources. PMID: 21612988 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894195 Sun, 22 May 2011 23:00:00 +0100 4894195 http://www.medworm.com/index.php?rid=4894196&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21602108%26dopt%3DAbstract Authors: Novarina D, Amara F, Lazzaro F, Plevani P, Muzi-Falconi M Cells respond to genotoxic insults by triggering a DNA damage checkpoint surveillance mechanism and by activating repair pathways. Recent findings indicate that the two processes are more related than originally thought. Here we discuss the mechanisms involved in responding to UV-induced lesions in different phases of the cell cycle and summarize the most recent data in a model where Nucleotide Excision Repair (NER) and exonucleolytic activities act in sequence leading to checkpoint activation in non replicating cells. The critical trigger is likely represented by problematic intermediates that cannot be completely or efficiently repaired by NER. In S phase cells, on the other hand, the replicative polymerases, blocked ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894196 Thu, 19 May 2011 23:00:00 +0100 4894196 http://www.medworm.com/index.php?rid=4894198&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21601535%26dopt%3DAbstract Authors: Sukhanova MV, D'Herin C, Auffret van der Kemp P, Koval VV, Boiteux S, Lavrik OI To characterize proteins that interact with base excision/single-strand interruption repair DNA intermediates in cell free extracts of Saccharomyces cerevisiae, we used a combination of photoaffinity labeling with the protein identification by MALDI-TOF-MS peptide mapping. Photoreactive analogue of dCTP, namely exo-N-[4-(4-azido-2,3,5,6,-tetrafluorobenzylidenehydrazinocarbonyl)-butylcarbamoyl]-2'-deoxycytidine-5'-triphosphate, and [(32)P]-labeled DNA duplex containing one nucleotide gap were used to generate nick-containing DNA with a photoreactive dCMP residue at the 3'-margin of the nick. This photoreactive DNA derivative was incubated with the yeast cell extract and after UV irradiation a number... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894198 Wed, 18 May 2011 23:00:00 +0100 4894198 http://www.medworm.com/index.php?rid=4894197&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21601536%26dopt%3DAbstract Authors: Lehmann AR The late steps of nucleotide excision repair, following incisions to remove the damaged section of DNA, comprise repair synthesis and ligation. In vitro and in vivo studies have shown the size of the repaired patch to be about 30 nucleotides. In vitro studies implicated the replicative polymerases in repair synthesis, but recent in vivo data have shown that several DNA polymerases and ligases are involved in these steps in human cells. PMID: 21601536 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894197 Wed, 18 May 2011 23:00:00 +0100 4894197 http://www.medworm.com/index.php?rid=4894200&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21600858%26dopt%3DAbstract We described how much of our mechanistic understanding of NER was derived from biochemical studies that analysed the repair reaction in DNA substrates not representative of that which exists in the living cell. We pointed out that our efforts to understand how NER operates in chromatin had been hampered in part because of the well-known inhibition of NER that occurs when DNA is assembled into nucleosomes and used as the substrate to examine the repair reaction in vitro. Despite this technical bottleneck, we summarized the biochemical, genetic and cell-based studies which have provided insights into the molecular mechanism of NER in the cellular context. More recently, we revisited the topic of how UV induced DNA damage is repaired in chromatin. In this review we examined the commonly held ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894200 Tue, 17 May 2011 23:00:00 +0100 4894200 http://www.medworm.com/index.php?rid=4894199&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21600859%26dopt%3DAbstract This article, taken largely from the book Correcting the Blueprint of Life: An Historical Account of the Discovery of DNA Repair Mechanisms, summarizes the very early history of the discovery of nucleotide excision repair. PMID: 21600859 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4894199 Tue, 17 May 2011 23:00:00 +0100 4894199 http://www.medworm.com/index.php?rid=4849083&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592868%26dopt%3DAbstract Authors: Fagbemi AF, Orelli B, Schärer OD Nucleotide excision repair (NER) is a DNA repair pathway that is responsible for removing a variety of lesions caused by harmful UV light, chemical carcinogens, and environmental mutagens from DNA. NER involves the concerted action of over 30 proteins that sequentially recognize a lesion, excise it in the form of an oligonucleotide, and fill in the resulting gap by repair synthesis. ERCC1-XPF and XPG are structure-specific endonucleases responsible for carrying out the incisions 5' and 3' to the damage respectively, culminating in the release of the damaged oligonucleotide. This review focuses on the recent work that led to a greater understanding of how the activities of ERCC1-XPF and XPG are regulated in NER to prevent unwanted cuts in DNA o... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849083 Sun, 15 May 2011 23:00:00 +0100 4849083 http://www.medworm.com/index.php?rid=4849075&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21592869%26dopt%3DAbstract Authors: Egly JM, Coin F The TFIIH multiprotein complex is organized into a 7-subunit core associated with a 3-subunit CDK-activating kinase module (CAK). Three enzymatic subunits are present in TFIIH, two ATP-dependent DNA helicases: XPB and XPD, and the kinase Cdk7. Mutations in three of the subunits, XPB, XPD and TTDA, lead to three distinct genetic disorders: xeroderma pigmentosum (XP), Cockayne syndrome (CS) and trichothiodystrophy (TTD) predisposing patients not only to cancer and ageing but also to developmental and neurological defects. These heterogeneous phenotypes originate from the dual role of TFIIH in transcription and DNA repair. For twenty years, many molecular studies have been conducted with the aim to unveil the role of TFIIH in DNA repair and transcription as well a... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849075 Sun, 15 May 2011 23:00:00 +0100 4849075 http://www.medworm.com/index.php?rid=4849095&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21571596%26dopt%3DAbstract Authors: Fuss JO, Tainer JA Helicases must unwind DNA at the right place and time to maintain genomic integrity or gene expression. Biologically critical XPB and XPD helicases are key members of the human TFIIH complex; they anchor CAK kinase (cyclinH, MAT1, CDK7) to TFIIH and open DNA for transcription and for repair of duplex distorting damage by nucleotide excision repair (NER). NER is initiated by arrested RNA polymerase or damage recognition by XPC-RAD23B with or without DDB1/DDB2. XP helicases, named for their role in the extreme sun-mediated skin cancer predisposition xeroderma pigmentosum (XP), are then recruited to asymmetrically unwind dsDNA flanking the damage. XPB and XPD genetic defects can also cause premature aging with profound neurological defects without increased can... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849095 Thu, 12 May 2011 23:00:00 +0100 4849095 http://www.medworm.com/index.php?rid=4849127&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21570926%26dopt%3DAbstract Authors: Milota M, Jones DL, Cleaver J, Jamall IS The past two decades of research into Xeroderma pigmentosum (XP), an autosomal recessive disease, has been marked by significant progress in understanding the molecular basis of this rare disease. More importantly, especially from the perspective of the affected families, is that this knowledge has been applied to diagnose the condition both in utero as well as in the very early days of life. The eight known XP genes and their different phenotypes present a number of challenges that the XP Workshop sponsored by the NIH in 2010 has highlighted. There is little current treatment specifically designed for any of the XP types other than standard dermatological and neurological evaluations and care. The Xeroderma Pigmentosum Family Support G... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849127 Wed, 11 May 2011 23:00:00 +0100 4849127 http://www.medworm.com/index.php?rid=4849134&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21570366%26dopt%3DAbstract Authors: Yang M, Aamodt RM, Dalhus B, Balasingham S, Helle I, Andersen P, Tønjum T, Alseth I, Rognes T, Bjørås M The ada operon of Mycobacterium tuberculosis, which encodes a composite protein of AdaA and AlkA and a separate AdaB/Ogt protein, was characterized. M. tuberculosis treated with N-methyl-N'-nitro-N-nitrosoguanidine induced transcription of the adaA-alkA and adaB genes, suggesting that M. tuberculosis mount an inducible response to methylating agents. Survival assays of the methyltransferase defective Escherichia coli mutant KT233 (ada ogt), showed that expression of the adaB gene rescued the alkylation sensitivity. Further, adaB but not adaA-alkA complemented the hypermutator phenotype of KT233. Purified AdaA-AlkA and AdaB possessed methyltransferase activity. These data ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849134 Tue, 10 May 2011 23:00:00 +0100 4849134 http://www.medworm.com/index.php?rid=4849139&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21565563%26dopt%3DAbstract Authors: Sebesta M, Burkovics P, Haracska L, Krejci L The error-free repair of double-strand DNA breaks by homologous recombination (HR) ensures genomic stability using undamaged homologous sequence to copy genetic information. While some of the aspects of the initial steps of HR are understood, the molecular mechanisms underlying events downstream of the D-loop formation remain unclear. Therefore, we have reconstituted D-loop-based in vitro recombination-associated DNA repair synthesis assay and tested the efficacy of polymerases Pol δ and Pol η to extend invaded primer, and the ability of three helicases (Mph1, Srs2 and Sgs1) to displace this extended primer. Both Pol δ and Pol η extended up to 50% of the D-loop substrate, but differed in product length and dependency on prolifer... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849139 Mon, 09 May 2011 23:00:00 +0100 4849139 http://www.medworm.com/index.php?rid=4849149&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561811%26dopt%3DAbstract Authors: Chakraborty P, Grosse F Human DHX9 helicase, also known as nuclear DNA helicase II (NDH II) and RNA helicase A (RHA), belongs to the SF2 superfamily of nucleic acid unwinding enzymes. DHX9 melts simple DNA-DNA, RNA-RNA, and DNA-RNA strands with a 3'-5' polarity; despite this little is known about its substrate specificity. Here, we used partial duplex DNA consisting of M13mp18 DNA and oligonucleotide-based replication and recombination intermediates. We show that DHX9 unwinds DNA- and RNA-containing forks, DNA- and RNA-containing displacement loops (D- and R-loops), and also G-quadruplexes. With these substrates, DHX9 behaved similarly as the RecQ helicase WRN. In contrast to WRN, DHX9 melted RNA-hybrids considerably faster than the corresponding DNA-DNA strands. DHX9 preferab... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849149 Sun, 08 May 2011 23:00:00 +0100 4849149 http://www.medworm.com/index.php?rid=4849144&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21561812%26dopt%3DAbstract Authors: Schärer OD PMID: 21561812 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849144 Sun, 08 May 2011 23:00:00 +0100 4849144 http://www.medworm.com/index.php?rid=4849158&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21550320%26dopt%3DAbstract Authors: Vermeulen W Despite detailed knowledge on the genetic network and biochemical properties of most of the nucleotide excision repair (NER) proteins, cell biological analysis has only recently made it possible to investigate the temporal and spatial organization of NER. In contrast to several other DNA damage response mechanisms that occur in specific subnuclear structures, NER is not confined to nuclear foci, which has severely hampered the analysis of its arrangement in time and space. In this review the recently developed tools to study the dynamic molecular transactions between the NER factors and the chromatin template are summarized. First, different procedures to inflict DNA damage in a part of the cell nucleus are discussed. In addition, technologies to measure protein dy... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849158 Thu, 05 May 2011 23:00:00 +0100 4849158 http://www.medworm.com/index.php?rid=4849153&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21550321%26dopt%3DAbstract Authors: Lauritzen KH, Cheng C, Wiksen H, Bergersen LH, Klungland A Mitochondria are highly dynamic organelles that can be actively transported within the cell to satisfy local requirements. They are vital for providing cellular energy, but are also an important endogenous source of reactive oxygen species. The distribution of mitochondria is particularly important for neurons because of the morphological complexity of these cells, and because neural processing is metabolically expensive. Defects in mitochondrial distribution, observed in several neurodegenerative diseases, can result in synaptic dysfunction. We have generated transgenic mice expressing an enzyme in forebrain neurons that causes mitochondrial DNA (mtDNA) damage in the form of abasic-sites, creating mtDNA toxicity. Here... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4849153 Thu, 05 May 2011 23:00:00 +0100 4849153 http://www.medworm.com/index.php?rid=4794869&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21474392%26dopt%3DAbstract Authors: Maiti A, Drohat AC Repair of G·T mismatches arising from deamination of 5-methylcytosine (m(5)C) involves excision of thymine and restoration of a G·C pair via base excision repair (BER). Thymine DNA glycosylase (TDG) is one of two mammalian enzymes that can specifically remove thymine from G·T mispairs. While TDG can excise other bases, it maintains stringent specificity for a CpG context, suggesting deaminated m(5)C is an important biological substrate. Recent studies reveal TDG is essential for embryogenesis; it helps to maintain an active chromatin complex and initiates BER to counter aberrant de novo CpG methylation, which may involve excision of actively deaminated m(5)C. The relatively weak G·T activity of TDG has been implicated in the hypermutability of CpG sites,... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794869 Wed, 04 May 2011 23:00:00 +0100 4794869 http://www.medworm.com/index.php?rid=4794867&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21493166%26dopt%3DAbstract Authors: Hays JB Two proteins that process damaged DNA may function in the same pathway, or in redundant ("synergistic") pathways that respond to the same lesion(s), or in parallel pathways targeted to different lesions. Previously, extended plots of positive outcomes (such as cell survival) or negative outcomes (such as reduced tissue growth) vs. genotoxic dose yielded empirical estimates of wt and mutant resistances to DNA damage. Recently, wt and mutant outcomes have been compared at one or two doses. The criterion for parallel pathways was "additivity": wt positive outcomes roughly equal to numerical sums of single-mutant positive outcomes or double-mutant negative outcomes equal to sums of single-mutant negative outcomes. For redundant pathways, wt positive outcomes or double-muta... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794867 Wed, 04 May 2011 23:00:00 +0100 4794867 http://www.medworm.com/index.php?rid=4794865&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21524605%26dopt%3DAbstract Authors: PMID: 21524605 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794865 Wed, 04 May 2011 23:00:00 +0100 4794865 http://www.medworm.com/index.php?rid=4794857&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21543268%26dopt%3DAbstract Authors: Huang Y, Hou H, Yi Q, Zhang Y, Chen D, Jiang E, Xia Y, Fenech M, Shi Q Micronuclei are closely related to DNA damage. The presence of micronuclei in mammalian cells is a common phenomenon post ionizing radiation. The level of micronucleation in tumor cells has been used to predict prognosis after radiotherapy in many cancers. In order to understand how irradiation-induced micronuclei affect cell fate, we performed extensive long-term live cell imaging on X-irradiated nasopharyngeal carcinoma (NPC) cells. To visualize the dynamics of micronuclei more clearly, chromosomes were stably labeled with red fluorescent protein (RFP) by targeting to human histone H2B. Initially, significantly more micronuclei were observed in radiosensitive cells than in radioresistant cells post irradi... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794857 Mon, 02 May 2011 23:00:00 +0100 4794857 http://www.medworm.com/index.php?rid=4794851&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21546323%26dopt%3DAbstract Authors: Mendez P, Taron M, Moran T, Fernandez MA, Requena G, Rosell R The host-cell reactivation assay (HCRA) is a functional assay that allows the identification of the genes responsible for DNA repair-deficient syndromes, such as Xeroderma pigmentosum, by cross-complementation experiments. It has also been used in molecular epidemiology studies to correlate the low nucleotide excision repair pathway function in peripheral blood lymphocytes with an increased risk of bladder, head and neck, skin and lung cancers. Herein, we present the technical validation of a newly modified HCRA, where nucleofection is used for the transfection of the pmaxGFP plasmid into cryopreserved peripheral blood lymphocytes (PBLs) or lymphoblastoid cell lines. In each sample, 20-24h after transfection, the re... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794851 Mon, 02 May 2011 23:00:00 +0100 4794851 http://www.medworm.com/index.php?rid=4794861&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21543267%26dopt%3DAbstract Authors: Say AF, Ledford LL, Sharma D, Singh AK, Leung WK, Sehorn HA, Tsubouchi H, Sung P, Sehorn MG Meiotic homologous recombination in Saccharomyces cerevisiae involves formation of nucleoprotein filaments of Rad51 and Dmc1 that mediate DNA strand exchange between homologous chromosomes. The Mei5-Sae3 protein complex functions as a recombination mediator to promote nucleation of the Dmc1 recombinase onto replication protein A-coated single-stranded DNA. Here, we have expressed and purified the Mei5 protein, Sae3 protein and the Mei5-Sae3 complex for biochemical studies. We show the Mei5-Sae3 complex preferentially binds a fork-like DNA substrate to 3' overhanging DNA, single-stranded DNA or double-stranded DNA. We demonstrate that Mei5 confers DNA binding activity to the Mei5-Sae3 co... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794861 Sun, 01 May 2011 23:00:00 +0100 4794861 http://www.medworm.com/index.php?rid=4794862&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21530420%26dopt%3DAbstract This study thus clarifies the relationships between the different pathways of DSB repair in the living plant and points to the existence of novel DSB repair processes. PMID: 21530420 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794862 Tue, 26 Apr 2011 23:00:00 +0100 4794862 http://www.medworm.com/index.php?rid=4794866&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21515092%26dopt%3DAbstract In this study, plasmid-based experiments demonstrate that ZRT1-mediated minisatellite alterations occur independently of chromosomal context or adenine auxotrophy, and confirmed the stationary phase timing of the events. To further examine the stationary phase specificity of ZRT1-mediated minisatellite alterations, we deleted ETR1 and POR1, genes that were previously shown to differentially affect the viability of quiescent or nonquiescent cells in stationary phase populations. These experiments revealed that minisatellite alterations in Δzrt1 mutants occur exclusively in quiescent stationary phase cells. Finally, we show that loss of ZRT1 stimulates alterations in a derivative of the human HRAS1 minisatellite. We propose that the mechanism of ZRT1-mediated minisatellite instability durin... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794866 Thu, 21 Apr 2011 23:00:00 +0100 4794866 http://www.medworm.com/index.php?rid=4794868&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21482201%26dopt%3DAbstract We report the first description of a very high incidence (around 1/5000) of black XP patients in the Mayotte population in the Indian Ocean. Among a cohort of 32 XP, we describe the clinical and genetic features of 18 living Comorian black XP patients. We discuss the remarkable clinical differences between white and black XPs. Skin and ocular abnormalities are remarkably precocious and severe XP phenotypes are recognized by the early ocular injuries. In our cohort, the first skin cancer appeared at a median age of 4.5 years with no neurological symptoms. Post-UV DNA repair, cell survival and genetic complementation assigned these patients to the XP group C. All patients exhibited a new G→C homozygous substitution at 3'-end of XPC intron 12 (IVS 12-1G>C) leading to the abolition of an ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4794868 Wed, 06 Apr 2011 23:00:00 +0100 4794868 http://www.medworm.com/index.php?rid=4628547&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21420025%26dopt%3DAbstract Authors: PMID: 21420025 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4628547 Thu, 24 Mar 2011 21:00:13 +0100 4628547 http://www.medworm.com/index.php?rid=4628548&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21414850%26dopt%3DAbstract Authors: Clark AB, Lujan SA, Kissling GE, Kunkel TA During DNA synthesis in vitro using dNTP and rNTP concentrations present in vivo, yeast replicative DNA polymerases α, δ and ɛ (Pols α, δ and ɛ) stably incorporate rNTPs into DNA. rNTPs are also incorporated during replication in vivo, and they are repaired in an RNase H2-dependent manner. In strains encoding a mutator allele of Pol ɛ (pol2-M644G), failure to remove rNMPs from DNA due to deletion of the RNH201 gene encoding the catalytic subunit of RNase H2, results in deletion of 2-5 base pairs in short repetitive sequences. Deletion rates depend on the orientation of the reporter gene relative to a nearby replication origin, suggesting that mutations result from rNMPs incorporated during replication. Here we demonstrate that ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4628548 Tue, 15 Mar 2011 00:00:00 +0100 4628548 http://www.medworm.com/index.php?rid=4628549&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21393072%26dopt%3DAbstract We present evidence that two conserved arginine residues in the ID contact the phosphate backbone of the DNA, leading to strand separation after the ATPase-driven movement of the ID's. Remarkably, deletion of the ID generated a phenotype in which UV-survival strongly depends on the presence of photolyase, indicating that UvrA and photolyase form a ternary complex on a CPD-lesion. The zinc-finger motif is shown to be important for the transfer of the damage recognition signal to the ATPase of UvrA. In the absence of this domain the coupling between DNA binding and ATP hydrolysis is completely lost. Mutation of the phenylalanine residue in the tip of the zinc-finger domain resulted in a protein in which the ATPase was already triggered when binding to an undamaged site. As the zinc-finger mo... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4628549 Tue, 08 Mar 2011 00:00:00 +0100 4628549 http://www.medworm.com/index.php?rid=4566450&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353186%26dopt%3DAbstract Authors: PMID: 21353186 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4566450 Mon, 07 Mar 2011 00:00:00 +0100 4566450 http://www.medworm.com/index.php?rid=4566448&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21354867%26dopt%3DAbstract Authors: Schorzman AN, Perera L, Cutalo-Patterson JM, Pedersen LC, Pedersen LG, Kunkel TA, Tomer KB Mismatch repair (MMR) corrects replication errors that would otherwise lead to mutations and, potentially, various forms of cancer. Among several proteins required for eukaryotic MMR, MutLα is a heterodimer comprised of Mlh1 and Pms1. The two proteins dimerize along their C-terminal domains (CTDs), and the CTD of Pms1 houses a latent endonuclease that is required for MMR. The highly conserved N-terminal domains (NTDs) independently bind DNA and possess ATPase active sites. Here we use two protein footprinting techniques, limited proteolysis and oxidative surface mapping, coupled with mass spectrometry to identify amino acids involved along the DNA-binding surface of the Pms1-NTD. Limite... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4566448 Fri, 25 Feb 2011 00:00:00 +0100 4566448 http://www.medworm.com/index.php?rid=4566449&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21353648%26dopt%3DAbstract Authors: Onyango DO, Naguleswaran A, Delaplane S, Reed A, Kelley MR, Georgiadis MM, Sullivan WJ DNA repair is essential for cell viability and proliferation. In addition to reactive oxygen produced as a byproduct of their own metabolism, intracellular parasites also have to manage oxidative stress generated as a defense mechanism by the host. The spontaneous loss of DNA bases due to hydrolysis and oxidative DNA damage in intracellular parasites is great, but little is known about the type of DNA repair machineries that exist in these early-branching eukaryotes. However, it is clear, processes similar to DNA base excision repair (BER) must exist to rectify spontaneous and host-mediated damage in Toxoplasma gondii. Here we report that T. gondii, an opportunistic protozoan pathogen, posse... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4566449 Wed, 23 Feb 2011 00:00:00 +0100 4566449 http://www.medworm.com/index.php?rid=4566451&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342792%26dopt%3DAbstract Authors: Rübe CE, Lorat Y, Schuler N, Schanz S, Wennemuth G, Rübe C The recognition and repair of DNA double-strand breaks (DSBs) occurs in the context of highly structured chromatin. Here, we established a transmission electron microscopy (TEM) approach to localize gold-labeled DSB repair components in different chromatin environments within the intact nuclear architecture of cells in irradiated mouse tissues. The ultra-high resolution of TEM offers the intriguing possibility of detecting core components of the DNA repair machinery at the single-molecule level and visualizing their molecular interactions with specific histone modifications. By labeling phosphorylated Ku70, which binds directly to broken DNA ends in preparation for rejoining, this TEM approach can monitor formation a... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4566451 Sun, 20 Feb 2011 00:00:00 +0100 4566451 http://www.medworm.com/index.php?rid=4512670&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21333614%26dopt%3DAbstract Authors: Kidane D, Dalal S, Keh A, Liu Y, Zelterman D, Sweasy JB Maintaining genome integrity in germ cells is important, given that the germ cells produce the next generation of offspring. Base excision repair is a DNA repair pathway that is responsible for the repair of most endogenous DNA damage. A key enzyme that functions in this repair pathway is DNA polymerase beta (Pol β). We previously used conditional gene targeting to engineer mice with sperm deleted of the Pol B gene, which encodes Pol β. We characterized mutagenesis in the sperm of these mice and compared it to wild-type and mice heterozygous for the Pol B gene. We found that sperm obtained that were heterozygously or homozygously deleted of the Pol B gene exhibited increased mutation frequencies compared to wild-type sp... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4512670 Wed, 16 Feb 2011 00:00:00 +0100 4512670 http://www.medworm.com/index.php?rid=4512672&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21317046%26dopt%3DAbstract In this study we showed that poly(ADP-ribosyl)ation, beyond phosphorylation, is involved in the regulation of Che-1 stabilization following DNA damage. We demonstrated that Che-1 accumulation upon doxorubicin treatment is reduced after the inhibition of PARP activity in HCT116 cells and in PARP-1 knock-out or silenced cells. In accordance, impairment in Che-1 accumulation by PARP inhibition reduced Che-1 occupancy at p21 promoter and affected the expression of the corresponding gene. Epistasis experiments showed that the effect of poly(ADP-ribosyl)ation on Che-1 stabilization is independent from ATM kinase activity. Indeed we demonstrated that Che-1 protein co-immunoprecipitates with ADP-ribose polymers and that PARP-1 directly interacts with Che-1, promoting its modification in vitro and ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4512672 Fri, 11 Feb 2011 00:00:00 +0100 4512672 http://www.medworm.com/index.php?rid=4512671&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21317047%26dopt%3DAbstract Authors: Mott C, Symington LS Recombination between inverted repeats is RAD52 dependent, but reduced only modestly in the rad51Δ mutant. RAD59 is required for RAD51-independent inverted-repeat recombination, but no clear mechanism for how recombination occurs in the absence of RAD51 has emerged. Because Rad59 is thought to function as an accessory factor for the single-strand annealing activity of Rad52 one possible mechanism for spontaneous recombination could be by strand annealing between repeats at a stalled replication fork. Here we demonstrate the importance of the Rad52 single-strand annealing activity for generating recombinants by showing suppression of the rad52Δ, rad51Δ rad52Δ and rad52Δ rad59Δ inverted-repeat recombination defects by the rfa1-D228Y mutation. In additi... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4512671 Fri, 11 Feb 2011 00:00:00 +0100 4512671 http://www.medworm.com/index.php?rid=4512673&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21315663%26dopt%3DAbstract Authors: Tichy ED, Liang L, Deng L, Tischfield J, Schwemberger S, Babcock G, Stambrook PJ Accumulation of mutations in embryonic stem (ES) cells would be detrimental to an embryo derived from these cells, and would adversely affect multiple organ systems and tissue types. ES cells have evolved multiple mechanisms to preserve genomic integrity that extend beyond those found in differentiated cell types. The present study queried whether mismatch repair (MMR) and base-excision repair (BER) may play a role in the maintenance of murine ES cell genomes. The MMR proteins Msh2 and Msh6 are highly elevated in mouse ES cells compared with mouse embryo fibroblasts (MEFs), as are Pms2 and Mlh1, albeit to a lesser extent. Cells transfected with an MMR reporter plasmid showed that MMR repair capaci... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4512673 Wed, 09 Feb 2011 00:00:00 +0100 4512673 http://www.medworm.com/index.php?rid=4455099&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21295263%26dopt%3DAbstract Authors: PMID: 21295263 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455099 Mon, 07 Feb 2011 00:00:00 +0100 4455099 http://www.medworm.com/index.php?rid=4455097&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21300576%26dopt%3DAbstract We report that BLM knockdown in both cell lines specifically increased the frequency of HR events that produced deletions by crossovers or single-strand annealing while leaving the frequency of gene conversions unchanged or reduced. We observed no change in the accuracy of individual HR events and no substantial alteration of the nature of individual NHEJ events when BLM expression was reduced. Our work provides the first direct evidence that BLM influences DSB repair pathway choice in human chromosomes and suggests that BLM deficiency can engender genomic instability by provoking an increased frequency of HR events of a potentially deleterious nature. PMID: 21300576 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455097 Sat, 05 Feb 2011 00:00:00 +0100 4455097 http://www.medworm.com/index.php?rid=4455098&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21296624%26dopt%3DAbstract This study underscores the importance of replication using published data in larger populations. PMID: 21296624 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455098 Fri, 04 Feb 2011 00:00:00 +0100 4455098 http://www.medworm.com/index.php?rid=4455100&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21292567%26dopt%3DAbstract In this study, we examined the physiological roles of H. pylori RecRO pathway in DNA recombinational repair. We characterized H. pylori single mutants in recR and in recO, genes in the putative gap repair recombination pathway, and an addA recO double mutant that is thus deficient in both pathways that initiate DNA recombinational repair. The recR or recO single mutants showed the same level of sensitivity to mitomycin C as the parent strain, suggesting that the RecRO pathway is not responsible for the repair of DNA double strand breaks. However, H. pylori recR and recO mutants are highly sensitive to oxidative stress and separately to acid stress, two major stress conditions that H. pylori encounters in its physiological niche. The complementation of the recR mutant restored the sensitivi... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455100 Tue, 01 Feb 2011 00:00:00 +0100 4455100 http://www.medworm.com/index.php?rid=4455101&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21288781%26dopt%3DAbstract This report summarizes 35 plenary lectures presented during this three-day symposium, with topics ranging from DNA damage checkpoint signaling, DNA repair, posttranslational protein modifications in DNA damage response (DDR) to DDR in ageing and cancer. This symposium stimulated extensive discussions on science and potential collaboration among the 230 participants. PMID: 21288781 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455101 Mon, 31 Jan 2011 00:00:00 +0100 4455101 http://www.medworm.com/index.php?rid=4455102&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21269891%26dopt%3DAbstract Authors: Krijger PH, Lee KY, Wit N, van den Berk PC, Wu X, Roest HP, Maas A, Ding H, Hoeijmakers JH, Myung K, Jacobs H DNA damage tolerance is regulated at least in part at the level of proliferating cell nuclear antigen (PCNA) ubiquitination. Monoubiquitination (PCNA-Ub) at lysine residue 164 (K164) stimulates error-prone translesion synthesis (TLS), Rad5-dependent polyubiquitination (PCNA-Ub(n)) stimulates error-free template switching (TS). To generate high affinity antibodies by somatic hypermutation (SHM), B cells profit from error-prone TLS polymerases. Consistent with the role of PCNA-Ub in stimulating TLS, hypermutated B cells of PCNA(K164R) mutant mice display a defect in generating selective point mutations. Two Rad5 orthologs, HLTF and SHPRH have been identified as alternati... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455102 Mon, 24 Jan 2011 00:00:00 +0100 4455102 http://www.medworm.com/index.php?rid=4455103&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21256093%26dopt%3DAbstract Authors: Paddock MN, Bauman AT, Higdon R, Kolker E, Takeda S, Scharenberg AM Affinity maturation of antibodies requires a unique process of targeted mutation that allows changes to accumulate in the antibody genes while the rest of the genome is protected from off-target mutations that can be oncogenic. This targeting requires that the same deamination event be repaired either by a mutagenic or a high-fidelity pathway depending on the genomic location. We have previously shown that the BRCT domain of the DNA-damage sensor PARP-1 is required for mutagenic repair occurring in the context of IgH and IgL diversification in the chicken B cell line DT40. Here we show that immunoprecipitation of the BRCT domain of PARP-1 pulls down Ku70 and the DNA-PK complex although the BRCT domain of PARP-... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4455103 Wed, 19 Jan 2011 00:00:00 +0100 4455103 http://www.medworm.com/index.php?rid=4388900&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21239234%26dopt%3DAbstract In this study, fluorescence resonance energy transfer (FRET) was used to monitor the heterology tolerance of human Rad51 mediated strand exchange reactions, in real time, by introducing either G-T or I-C mismatched base pairs between the two homologous DNA strands. The strand exchange reactions were much more sensitive to G-T than to I-C base pairs. These results imply that the recognition of homology and the tolerance of heterology by hRad51 may depend on the local structural motif adopted by the base pairs participating in strand exchange. AnhRad51 mutant protein (hRad51K133R), deficient in ATP hydrolysis, showed greater heterology tolerance to both types of mismatch base pairing, suggesting that ATPase activity may be important for maintenance of high fidelity homologous recombination D... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4388900 Fri, 14 Jan 2011 00:00:00 +0100 4388900 http://www.medworm.com/index.php?rid=4388902&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21237724%26dopt%3DAbstract Authors: Rosenberger A, Rössler U, Hornhardt S, Sauter W, Bickeböller H, Wichmann HE, Gomolka M The COMET assay is recognized as a rapid and sensitive method in quantifying radiation induced DNA damage. We investigated the distorting influence of endogenous, assay-inherent factors onto base (single cell level) and primary outcome measures (experimental/slide level), such as olive tail moment (OTM) and percentage DNA in the tail (%tail-DNA). From 2003 to 2008, we performed the assay on lymphocytes isolated from the blood samples of 355 lung cancer patients, 170 controls, and 610 relatives, as well as one single reference individual, repeated 170 times. In total, the data from 10,016 single experiments containing around 1,750,000 cells have been included in this study. This is the firs... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4388902 Thu, 13 Jan 2011 00:00:00 +0100 4388902 http://www.medworm.com/index.php?rid=4388901&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21237725%26dopt%3DAbstract Authors: Shcherbakov VP, Plugina L, Shcherbakova T In previous papers we described an extra recombination mechanism in T4 phage, which contributed to general recombination only when particular mutations were used as geneticmarkers (high recombination or HR markers), whereas it was practically inactive towards other rIIB mutations (low recombination or LR markers). This marker-dependent recombination pathway was identified as a repair of mismatches in recombination heteroduplexes. We suggested that the first step in this pathway, recognition and incision of the mismatch, is performed by endonuclease VII (endo VII) encoded by the T4 gene 49. In the present paper, we tested this hypothesis in vivo. We used an experimental model system that combines site-specific double-strand breaks with ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4388901 Thu, 13 Jan 2011 00:00:00 +0100 4388901 http://www.medworm.com/index.php?rid=4388905&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227757%26dopt%3DAbstract Authors: Matsumoto Y, Miyamoto T, Sakamoto H, Izumi H, Nakazawa Y, Ogi T, Tahara H, Oku S, Hiramoto A, Shiiki T, Fujisawa Y, Ohashi H, Sakemi Y, Matsuura S MRE11 and NBS1 function together as components of a MRE11/RAD50/NBS1 protein complex, however deficiency of either protein does not result in the same clinical features. Mutations in the NBN gene underlie Nijmegen breakage syndrome (NBS), a chromosomal instability syndrome characterized by microcephaly, bird-like faces, growth and mental retardation, and cellular radiosensitivity. Additionally, mutations in the MRE11A gene are known to lead to an ataxia-telangiectasia-like disorder (ATLD), a late-onset, slowly progressive variant of ataxia-telangiectasia without microcephaly. Here we describe two unrelated patients with NBS-like sev... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4388905 Mon, 10 Jan 2011 00:00:00 +0100 4388905 http://www.medworm.com/index.php?rid=4388904&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227758%26dopt%3DAbstract Authors: Wiltrout ME, Walker GC Translesion DNA synthesis (TLS) functions as a tolerance mechanism for DNA damage at a potentially mutagenic cost. Three TLS polymerases (Pols) function to bypass DNA damage in Saccharomyces cerevisiae: Rev1, Pol ζ, a heterodimer of the Rev3 and Rev7 proteins, and Pol η (Rad30). Our lab has shown that S. cerevisiae Rev1 protein levels are under striking cell cycle regulation, being ∼50-fold higher during G2/M than during G1 and much of S phase (Waters and Walker, 2006). REV1 transcript levels only vary ∼3-fold in a similar cell cycle pattern, suggesting a posttranscriptional mechanism controls protein levels. Here, we show that the S. cerevisiae Rev1 protein is unstable during both the G1 and the G2/M phases of the cell cycle, however, the protein'... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4388904 Mon, 10 Jan 2011 00:00:00 +0100 4388904 http://www.medworm.com/index.php?rid=4388903&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21227759%26dopt%3DAbstract Authors: Mimitou EP, Symington LS Homology-dependent repair of DNA double-strand breaks (DSBs) initiates by the 5'-3' resection of the DNA ends to create single-stranded DNA (ssDNA), the substrate for Rad51/RecA binding. Long tracts of ssDNA are also required for activation of the ATR-mediated checkpoint response. Thus, identifying the proteins required and the underlying mechanism for DNA end resection has been an intense area of investigation. Genetic studies in Saccharomyces cerevisiae show that end resection takes place in two steps. Initially, a short oligonucleotide tract is removed from the 5' strand to create an early intermediate with a short 3' overhang. Then in a second step the early intermediate is rapidly processed generating an extensive tract of ssDNA. The first step is... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4388903 Mon, 10 Jan 2011 00:00:00 +0100 4388903 http://www.medworm.com/index.php?rid=4299004&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21186010%26dopt%3DAbstract Authors: PMID: 21186010 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4299004 Thu, 30 Dec 2010 22:47:45 +0100 4299004 http://www.medworm.com/index.php?rid=4299005&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21183410%26dopt%3DAbstract Authors: Vejrup-Hansen R, Mizuno K, Miyabe I, Fleck O, Holmberg C, Murray JM, Carr AM, Nielsen O In both Schizosaccharomyces pombe and Saccharomyces cerevisiae, Mms22 and Mms1 form a complex with important functions in the response to DNA damage, loss of which leads to perturbations during replication. Furthermore, in S. cerevisiae, Mms1 has been suggested to function in concert with a Cullin-like protein, Rtt101/Cul8, a potential paralog of Cullin 4. We performed epistasis analysis between Δmms1 and mutants of pathways with known functions in genome integrity, and measured the recruitment of homologous recombination proteins to blocked replication forks and recombination frequencies. We show that, in S. pombe, the functions of Mms1 and the conserved components of the Cullin 4 ubiquit... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4299005 Tue, 21 Dec 2010 00:00:00 +0100 4299005 http://www.medworm.com/index.php?rid=4299006&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21146476%26dopt%3DAbstract Authors: Hodgson A, Terentyev Y, Johnson RA, Bishop-Bailey A, Angevin T, Croucher A, Goldman AS During meiosis DNA double-strand breaks (DSBs) are induced and repaired by homologous recombination to create gene conversion and crossover products. Mostly these DSBs are made by Spo11, which covalently binds to the DSB ends. More rarely in Saccharomyces cerevisiae, other meiotic DSBs are formed by self-homing endonucleases such as VDE, which is site specific and does not covalently bind to the DSB ends. We have used experimentally located VDE-DSB sites to analyse an intermediate step in homologous recombination, resection of the single-strand ending 5' at the DSB site. Analysis of strains with different mutant alleles of MRE11 (mre11-58S and mre11-H125N) and deleted for EXO1 indicated that... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4299006 Mon, 13 Dec 2010 00:00:00 +0100 4299006 http://www.medworm.com/index.php?rid=4243705&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21115283%26dopt%3DAbstract Authors: Hiom K The repair of DNA double strand breaks (dsb) is important for maintaining the physical and genetic integrity of the genome. Moreover, in humans it is associated with the prevention of diseases such as immune deficiencies and cancer. This review briefly explores the fundamental strategies for repairing dsb, examines how cells maximize the fidelity of dsb repair in the cell cycle and discusses the requirements for dsb repair in the context of chromatin. PMID: 21115283 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243705 Thu, 09 Dec 2010 21:20:29 +0100 4243705 http://www.medworm.com/index.php?rid=4243701&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130713%26dopt%3DAbstract Authors: Palomera-Sanchez Z, Zurita M Due to its link with human pathologies, including cancer, the mechanism of Nucleotide Excision Repair (NER) has been extensively studied. Most of the pathway and players have been defined using in vitro reconstitution experiments. However, in vivo, the NER machinery must deal with the presence of organized chromatin, which in some regions, such as heterochromatin, is highly condensed but still susceptible to DNA damage. A series of events involving different chromatin-remodeling factors and histone-modifying enzymes target chromatin regions that contain DNA lesions. CPDs change the structure of the nucleosome, allowing access to factors that can recognize the lesion. Next, DDB1-DDB2 protein complexes, which mono-ubiquitinate histones H2A, H3, and H... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243701 Thu, 02 Dec 2010 00:00:00 +0100 4243701 http://www.medworm.com/index.php?rid=4243700&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130714%26dopt%3DAbstract Authors: Horton JK, Stefanick DF, Zeng JY, Carrozza MJ, Wilson SH Treatment of PARP-1-expressing cells with the combination of a DNA methylating agent (MMS) and the PARP inhibitor 4-amino-1,8-naphthalimide (4-AN) leads to an ATR/Chk1-dependent S phase checkpoint and cell death by apoptosis. Activation of ATM/Chk2 is involved in sustaining the S phase checkpoint, and double strand break (DSB) accumulation was demonstrated. NBS1, part of the MRN complex that responds to DSBs, is known to modulate ATR- and ATM-dependent checkpoint responses to UV and IR, but a role in the response to PARP inhibition has not been addressed. Here we show that the S phase checkpoint observed 4-8h after MMS+4-AN treatment was absent in cells deficient in NBS1, but was present in NBS1-complemented (i.e., funct... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243700 Thu, 02 Dec 2010 00:00:00 +0100 4243700 http://www.medworm.com/index.php?rid=4243699&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130715%26dopt%3DAbstract Authors: Blackford AN, Stewart GS Non-degradative ubiquitylation plays a crucial role in many cellular signaling pathways, including the DNA damage response. Two ubiquitin ligases, RNF8 and RNF168, in combination with the E2 ubiquitin conjugating enzyme UBC13 catalyze the formation of K63-linked ubiquitin chains at sites of DNA double-strand breaks to promote their faithful repair. However, little is known about their negative regulation. A recent study identifies a deubiquitylating enzyme, OTUB1, which counteracts RNF8/RNF168-dependent ubiquitin chain formation at break sites. Surprisingly, this enzyme carries out its function not by cleavage of polyubiquitin chains, but by targeting UBC13. This non-canonical role for a deubiquitylating enzyme has implications for the regulation of ub... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243699 Thu, 02 Dec 2010 00:00:00 +0100 4243699 http://www.medworm.com/index.php?rid=4243702&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21130053%26dopt%3DAbstract Authors: Germann SM, Oestergaard VH, Haas C, Salis P, Motegi A, Lisby M DPB11/TopBP1 is an essential evolutionarily conserved gene involved in initiation of DNA replication and checkpoint signaling. Here, we show that Saccharomyces cerevisiae Dpb11 forms nuclear foci that localize to sites of DNA damage in G1, S and G2 phase, a recruitment that is conserved for its homologue TopBP1 in Gallus gallus. Damage-induced Dpb11 foci are distinct from Sld3 replication initiation foci. Further, Dpb11 foci are dependent on the checkpoint proteins Mec3 (9-1-1 complex) and Rad24, and require the C-terminal domain of Dpb11. Dpb11 foci are independent of the checkpoint kinases Mec1 and Tel1, and of the checkpoint mediator Rad9. In a site-directed mutagenesis screen, we identify a separation-of-functi... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243702 Wed, 01 Dec 2010 00:00:00 +0100 4243702 http://www.medworm.com/index.php?rid=4243704&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21123118%26dopt%3DAbstract Authors: Rahn JJ, Rowley B, Lowery MP, Coletta LD, Limanni T, Nairn RS, Adair GM The ERCC1-XPF structure-specific endonuclease is necessary for correct processing of homologous recombination intermediates requiring the removal of end-blocking nonhomologies. We previously showed that targeting the endogenous CHO APRT locus with plasmids designed to generate such intermediates revealed defective recombination phenotypes in ERCC1 deficient cells, including suppression of targeted insertion and vector correction recombinants and the generation of a novel class of aberrant recombinants through a deletogenic mechanism. In the present study, we examined some of the mechanistic features of ERCC1-XPF in processing recombination intermediates by varying gene targeting parameters. These included ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243704 Mon, 29 Nov 2010 00:00:00 +0100 4243704 http://www.medworm.com/index.php?rid=4243703&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21123119%26dopt%3DAbstract Authors: Rübe CE, Zhang S, Miebach N, Fricke A, Rübe C Spermatogonial stem cells (SSCs) must maintain the integrity of their genome to prevent reproduction failure and limit the hereditary risk associated with transmission to the progeny. SSCs must therefore have robust response mechanisms to counteract the potentially deleterious effects of DNA damage, with DNA double-strand breaks (DSBs) representing the greatest threat to genomic integrity. Through in vivo analysis of the DNA damage response of SSCs within their physiological tissue context, we aimed to gain insights into the mechanisms by which SSCs preserve genome integrity. After whole-body irradiation of repair-proficient and repair-deficient (DNA-PK- and ATM-deficient) mice, the formation and rejoining of DSBs was analyzed in... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4243703 Mon, 29 Nov 2010 00:00:00 +0100 4243703 http://www.medworm.com/index.php?rid=4211905&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112818%26dopt%3DAbstract Authors: Friedberg EC PMID: 21112818 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4211905 Fri, 26 Nov 2010 00:00:00 +0100 4211905 http://www.medworm.com/index.php?rid=4211906&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21112256%26dopt%3DAbstract Authors: De Amicis A, Piane M, Ferrari F, Fanciulli M, Delia D, Chessa L Ataxia with oculomotor apraxia type 2 (AOA2) is an autosomal recessive neurodegenerative disorder characterized by cerebellar ataxia and oculomotor apraxia. The gene mutated in AOA2, SETX, encodes senataxin (SETX), a putative DNA/RNA helicase. The presence of the helicase domain led us to investigate whether SETX might play a role in DNA damage repair and telomere stability. We analyzed the response of AOA2 lymphocytes and lymphoblasts after treatment with camptothecin (CPT), mitomycin C (MMC), H(2)O(2) and X-rays by cytogenetic and Q-FISH (quantitative-FISH) assays. The rate of chromosomal aberrations was normal in AOA2 cells after treatment with CPT, MMC, H(2)O(2) and X-rays. Conversely, Q-FISH analysis showed c... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4211906 Thu, 25 Nov 2010 00:00:00 +0100 4211906 http://www.medworm.com/index.php?rid=4211907&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21111690%26dopt%3DAbstract Authors: Arczewska KD, Baumeier C, Kassahun H, Sengupta T, Bjørås M, Kuśmierek JT, Nilsen H MutT enzymes prevent DNA damage by hydrolysis of 8-oxodGTP, an oxidized substrate for DNA synthesis and antimutagenic, anticarcinogenic, and antineurodegenerative functions of MutT enzymes are well established. MutT has been found in almost all kingdoms of life, including many bacterial species, yeasts, plants and mammals. However, a Caenorhabditis elegans MutT homologue was not previously identified. Here, we demonstrate that NDX-4 exhibits both hallmarks of a MutT-type enzyme with an ability to hydrolyze 8-oxodGTP and suppress the Escherichia coli mutT mutator phenotype. Moreover, we show that NDX-4 contributes to genomic stability in vivo in C. elegans. Phenotypic analyses of an ndx-4 muta... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4211907 Wed, 24 Nov 2010 00:00:00 +0100 4211907 http://www.medworm.com/index.php?rid=4211908&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21109493%26dopt%3DAbstract Authors: Tumini E, Plevani P, Muzi-Falconi M, Marini F Fanconi anemia (FA) is an inherited disease characterized by bone marrow failure, increased cancer risk and hypersensitivity to DNA cross-linking agents, implying a role for this pathway in the maintenance of genomic stability. The central player of the FA pathway is the multi-subunit E3 ubiquitin ligase complex activated through a replication- and DNA damage-dependent mechanism. A consequence of the activation of the complex is the monoubiquitylation of FANCD2 and FANCI, late term effectors in the maintenance of genome integrity. The details regarding the coordination of the FA-dependent response and the DNA replication process are still mostly unknown. We found, by yeast two-hybrid assay and co-immunoprecipitation in human cells,... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4211908 Tue, 23 Nov 2010 00:00:00 +0100 4211908 http://www.medworm.com/index.php?rid=4180572&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21074501%26dopt%3DAbstract Authors: Martín CM, Guzmán EC Thymine deprivation results in the loss of viability in cells from bacteria to eukaryotes. Numerous studies have identified a variety of molecular processes and cellular responses associated with thymineless death (TLD). It has been observed that TLD occurs in actively growing cells, and DNA damage and DNA recombination structures have been associated with cells undergoing TLD. We measured the loss of viability in thymine-starved cells differing in the number of overlapping replication cycles (n), and we found that the magnitude of TLD correlates with the number of replication forks. By using pulsed field gel electrophoresis (PFGE), we determined the proportion of linear DNA (DSBs) and the amount of DNA remaining in the well after treatment with XbaI (nm... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4180572 Wed, 10 Nov 2010 00:00:00 +0100 4180572 http://www.medworm.com/index.php?rid=4134606&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21040889%26dopt%3DAbstract Authors: PMID: 21040889 [PubMed - in process] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4134606 Fri, 05 Nov 2010 07:25:09 +0100 4134606 http://www.medworm.com/index.php?rid=4134605&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21044871%26dopt%3DAbstract Authors: Keelagher RE, Cotton VE, Goldman AS, Borts RH Exo1 is a member of the Rad2 protein family and possesses both 5'-3' exonuclease and 5' flap endonuclease activities. In addition to performing a variety of functions during mitotic growth, Exo1 is also important for the production of crossovers during meiosis. However, its precise molecular role has remained ambiguous and several models have been proposed to account for the crossover deficit observed in its absence. Here, we present physical evidence that the nuclease activity of Exo1 is essential for normal 5'-3' resection at the Spo11-dependent HIS4 hotspot in otherwise wild-type cells. This same activity was also required for normal levels of gene conversion at the locus. However, gene conversions were frequently observed at a ... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4134605 Sun, 31 Oct 2010 00:00:00 +0100 4134605 http://www.medworm.com/index.php?rid=4134608&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21036673%26dopt%3DAbstract Authors: Goodarzi AA, Jeggo P, Lobrich M DNA non-homologous end-joining (NHEJ) and homologous recombination (HR) represent the major DNA double strand break (DSB) pathways in mammalian cells, whilst ataxia telangiectasia mutated (ATM) lies at the core of the DSB signalling response. ATM signalling plays a major role in modifying chromatin structure in the vicinity of the DSB and increasing evidence suggests that this function influences the DSB rejoining process. DSBs have long been known to be repaired with two (or more) component kinetics. The majority (∼85%) of DSBs are repaired with fast kinetics in a predominantly ATM-independent manner. In contrast, ∼15% of radiation-induced DSBs are repaired with markedly slower kinetics via a process that requires ATM and those mediator pro... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4134608 Fri, 29 Oct 2010 00:00:00 +0100 4134608 http://www.medworm.com/index.php?rid=4134607&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21036674%26dopt%3DAbstract Authors: López-Contreras AJ, Fernandez-Capetillo O Replication comes with a price. The molecular gymnastics that occur on DNA during its duplication frequently derive to a wide spectrum of abnormalities which are still far from understood. These are brought together under the unifying term "replicative stress" (RS) which likely stands for large and unprotected regions of single-stranded DNA (ssDNA). In addition to RS, recombinogenic stretches of ssDNA are also formed at resected DNA double strand breaks (DSBs). Both situations converge on a ssDNA intermediate, which is the triggering signal for a damage situation. The cellular response in both cases is coordinated by a phosphorylation-based signaling cascade that starts with the activation of the ATR (ATM and Rad3-related) kinase. Giv... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4134607 Fri, 29 Oct 2010 00:00:00 +0100 4134607 http://www.medworm.com/index.php?rid=4134610&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035407%26dopt%3DAbstract Authors: Williams GJ, Lees-Miller SP, Tainer JA Repair and integrity of DNA ends at breaks, replication forks and telomeres are essential for life; yet, paradoxically, these responses are, in many cases, controlled by a single protein complex, Mre11-Rad50-Nbs1 (MRN). The MRN complex consists of dimers of each subunit and this heterohexamer controls key sensing, signaling, regulation, and effector responses to DNA double-strand breaks including ATM activation, homologous recombinational repair, microhomology-mediated end joining and, in some organisms, non-homologous end joining. We propose that this is possible because each MRN subunit can exist in three or more distinct states; thus, the trimer of MRN dimers can exist in a stunning 6(3) or 216 states, a number that can be expanded fur... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4134610 Wed, 27 Oct 2010 00:00:00 +0100 4134610 http://www.medworm.com/index.php?rid=4134609&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21035408%26dopt%3DAbstract Authors: Bekker-Jensen S, Mailand N DNA double-strand breaks (DSBs) are among the most cytotoxic types of DNA damage, which if left unrepaired can lead to mutations or gross chromosomal aberrations, and promote the onset of diseases associated with genomic instability such as cancer. One of the most discernible hallmarks of the cellular response to DSBs is the accumulation and local concentration of a plethora of DNA damage signaling and repair proteins in the vicinity of the lesion, initiated by ATM-mediated phosphorylation of H2AX (γ-H2AX) and culminating in the generation of distinct nuclear compartments, so-called Ionizing Radiation-Induced Foci (IRIF). The assembly of proteins at the DSB-flanking chromatin occurs in a highly ordered and strictly hierarchical fashion. To a large e... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4134609 Wed, 27 Oct 2010 00:00:00 +0100 4134609 http://www.medworm.com/index.php?rid=4121002&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030320%26dopt%3DAbstract Authors: Evans TJ, Yamamoto KN, Hirota K, Takeda S Chemicals used industrially and commercially are required by law to be assessed for their genotoxic potential. However, all currently used assays have major limitations and despite intense effort, there is no universal agreement on which tests should be employed, or how to interpret results. We have developed a new assay system using the chicken DT40 B cell line that offers a number of significant advantages over current methodologies. Our assay could provide enhanced sensitivity using genetically defined and phenotypically characterized mutants defective in DNA repair pathways. Furthermore, analysis of the mutants, using DNA repair proficient wild-type cells as a negative control, minimizes false negative outcomes. Assessing the diffe... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4121002 Tue, 26 Oct 2010 00:00:00 +0100 4121002 http://www.medworm.com/index.php?rid=4121001&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030321%26dopt%3DAbstract Authors: Dobbs TA, Tainer JA, Lees-Miller SP The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and Ku heterodimer together form the biologically critical DNA-PK complex that plays key roles in the repair of ionizing radiation-induced DNA double-strand breaks through the non-homologous end-joining (NHEJ) pathway. Despite elegant and informative electron microscopy studies, the mechanism by which DNA-PK co-ordinates the initiation of NHEJ has been enigmatic due to limited structural information. Here, we discuss how the recently described small angle X-ray scattering structures of full-length Ku heterodimer and DNA-PKcs in solution, combined with a breakthrough DNA-PKcs crystal structure, provide significant insights into the early stages of NHEJ. Dynamic structural changes a... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4121001 Tue, 26 Oct 2010 00:00:00 +0100 4121001 http://www.medworm.com/index.php?rid=4121000&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21030322%26dopt%3DAbstract Authors: Mancebo E, Recio MJ, Martínez-Busto E, González-Granado LI, Rojo P, Fernández-Díaz E, Ruiz-Contreras J, Paz-Artal E, Allende LM PMID: 21030322 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4121000 Tue, 26 Oct 2010 00:00:00 +0100 4121000 http://www.medworm.com/index.php?rid=4106605&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971688%26dopt%3DAbstract Authors: Li S Base excision repair (BER) of dimethyl sulfate induced N-methylpurines (NMPs) was measured at nucleotide resolution in the mitochondrial DNA (mtDNA) of cultured human and yeast (Saccharomyces cerevisiae) cells. NMPs were repaired with heterogeneous rates in the human mtDNA. The nearest-neighbor nucleotides significantly affected the repair rates: NMPs between pyrimidines were repaired much faster than those between purines, and those between a purine and a pyrimidine were repaired at intermediate rates. Repair intermediates of NMPs can also be detected at certain sites of the human mtDNA, indicating an ineffectiveness of processing the intermediates at these sites by the human mitochondrial BER machinery. In contrast to the human mtDNA, the yeast mtDNA did not show detect... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106605 Thu, 21 Oct 2010 23:00:00 +0100 4106605 http://www.medworm.com/index.php?rid=4106607&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971042%26dopt%3DAbstract Authors: Holthausen JT, Wyman C, Kanaar R Homologous recombination, the exchange of DNA strands between homologous DNA molecules, is involved in repair of many structural diverse DNA lesions. This versatility stems from multiple ways in which homologous DNA strands can be rearranged. At the core of homologous recombination are recombinase proteins such as RecA and RAD51 that mediate homology recognition and DNA strand exchange through formation of a dynamic nucleoprotein filament. Four stages in the life cycle of nucleoprotein filaments are filament nucleation, filament growth, homologous DNA pairing and strand exchange, and filament dissociation. Progression through this cycle requires a sequence of recombinase-DNA and recombinase protein-protein interactions coupled to ATP binding an... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106607 Wed, 20 Oct 2010 23:00:00 +0100 4106607 http://www.medworm.com/index.php?rid=4106606&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20971043%26dopt%3DAbstract Authors: Ting L, Jun H, Junjie C Maintenance of genome stability depends on efficient and accurate repair of DNA lesions. Failure to properly repair damaged DNA can cause cell death, mutations and chromosomal instability, which eventually lead to tumorigenesis. The E3 ligase RAD18 is well-known for its function in DNA damage bypass and post-replication repair (PRR) in yeast and vertebrates via its ability to facilitate PCNA mono-ubiquitination at stalled replication forks. However, emerging evidence has also indicated that RAD18 plays an important role in homologous recombination (HR) in mammalian cells, which is an error-free DNA repair pathway that mediates the repair of double-strand breaks (DSBs). Here, we review how RAD18 carries out these distinct functions in response to differe... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106606 Wed, 20 Oct 2010 23:00:00 +0100 4106606 http://www.medworm.com/index.php?rid=4106608&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20970388%26dopt%3DAbstract Authors: Liberti SE, Andersen SD, Wang J, May A, Miron S, Perderiset M, Keijzers G, Nielsen FC, Charbonnier JB, Bohr VA, Rasmussen LJ Human exonuclease 1 (hEXO1) is implicated in DNA metabolism, including replication, recombination and repair, substantiated by its interactions with PCNA, DNA helicases BLM and WRN, and several DNA mismatch repair (MMR) proteins. We investigated the sub-nuclear localization of hEXO1 during S-phase progression and in response to laser-induced DNA double strand breaks (DSBs). We show that hEXO1 and PCNA co-localize in replication foci. This apparent interaction is sustained throughout S-phase. We also demonstrate that hEXO1 is rapidly recruited to DNA DSBs. We have identified a PCNA interacting protein (PIP-box) region on hEXO1 located in its COOH-terminal... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106608 Tue, 19 Oct 2010 23:00:00 +0100 4106608 http://www.medworm.com/index.php?rid=4106609&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20961817%26dopt%3DAbstract Authors: Brown JA, Pack LR, Sanman LE, Suo Z The base excision repair (BER) pathway coordinates the replacement of 1-10 nucleotides at sites of single-base lesions. This process generates DNA substrates with various gap sizes which can alter the catalytic efficiency and fidelity of a DNA polymerase during gap-filling DNA synthesis. Here, we quantitatively determined the substrate specificity and base substitution fidelity of human DNA polymerase λ (Pol λ), an enzyme proposed to support the known BER DNA polymerase β (Pol β), as it filled 1-10-nucleotide gaps at 1-nucleotide intervals. Pol λ incorporated a correct nucleotide with relatively high efficiency until the gap size exceeded 9 nucleotides. Unlike Pol λ, Pol β did not have an absolute threshold on gap size as the catalyti... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106609 Mon, 18 Oct 2010 23:00:00 +0100 4106609 http://www.medworm.com/index.php?rid=4106610&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20956092%26dopt%3DAbstract Authors: Jeggo PA PMID: 20956092 [PubMed - as supplied by publisher] (Source: DNA Repair) DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106610 Fri, 15 Oct 2010 23:00:00 +0100 4106610 http://www.medworm.com/index.php?rid=4106611&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20952260%26dopt%3DAbstract Authors: Pence MG, Blans P, Zink CN, Fishbein JC, Perrino FW The efficiency and fidelity of nucleotide incorporation and next-base extension by DNA polymerase (pol) κ past N(2)-ethyl-Gua were measured using steady-state and rapid kinetic analyses. DNA pol κ incorporated nucleotides and extended 3' termini opposite N(2)-ethyl-Gua with measured efficiencies and fidelities similar to that opposite Gua indicating a role for DNA pol κ at the insertion and extension steps of N(2)-ethyl-Gua bypass. The DNA pol κ was maximally activated to similar levels by a twenty-fold lower concentration of Mn(2+) compared to Mg(2+). In addition, the steady state analysis indicated that high fidelity DNA pol κ-catalyzed N(2)-ethyl-Gua bypass is Mg(2+)-dependent. Strikingly, Mn(2+) activation of DNA pol... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106611 Thu, 14 Oct 2010 23:00:00 +0100 4106611 http://www.medworm.com/index.php?rid=4106613&cid=s_35522_50_f&fid=35522&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20951652%26dopt%3DAbstract Authors: Shcherbakov VP, Plugina L, Shcherbakova T, Sizova S, Kudryashova E The double-strand break (DSB) repair via homologous recombination is generally construed as a high-fidelity process. However, some molecular genetic observations show that the recombination and the recombinational DSB repair may be mutagenic and even highly mutagenic. Here we developed an effective and precise method for studying the fidelity of DSB repair in vivo by combining DSBs produced site-specifically by the SegC endonuclease with the famous advantages of the recombination analysis of bacteriophage T4 rII mutants. The method is based on the comparison of the rate of reversion of rII mutation in the presence and in the absence of a DSB repair event initiated in the proximity of the mutation. We observed t... DNA Repair journals http://www.medworm.com/rss/comments.php?id=4106613 Wed, 13 Oct 2010 23:00:00 +0100 4106613