Mutation Research/DNA Repair最新文献

{"title":"Repair activities of 8-oxoguanine DNA glycosylase from Archaeoglobus fulgidus, a hyperthermophilic archaeon","authors":"Ji Hyung Chung ,&nbsp;Moo-Jin Suh ,&nbsp;Young In Park ,&nbsp;John A. Tainer ,&nbsp;Ye Sun Han","doi":"10.1016/S0921-8777(01)00081-7","DOIUrl":"10.1016/S0921-8777(01)00081-7","url":null,"abstract":"<div><p><span>Oxidative DNA damage is caused by reactive oxygen species<span> formed in cells as by products of aerobic metabolism<span> or of oxidative stress<span>. The 8-oxoguanine (8-oxoG) DNA glycosylase from </span></span></span></span><span><em>Archaeoglobus fulgidus</em></span> (<em>Af</em><span>ogg), which excises an oxidatively-damaged form of guanine, was overproduced in </span><em>Escherichia coli</em>, purified and characterized. <em>A. fulgidus</em> is a sulfate-reducing archaeon, which grows at between 60 and 95°C, with an optimum growth at 83°C. The <em>Af</em><span><span><span>ogg enzyme has both DNA glycosylase and apurinic/apyrimidinic (AP) lyase activities, with the latter proceeding through a </span>Schiff base intermediate. As expected for a protein from a hyperthermophilic organism, the </span>enzyme activity is optimal near pH 8.5 and 60°C, denaturing at 80°C, and is thermally stable at high levels of salt (500</span> <!-->mM). The <em>Af</em>ogg protein efficiently cleaves oligomers containing 8-oxoG:C and 8-oxoG:G base pairs, and is less effective on oligomers containing 8-oxoG:T and 8-oxoG:A mispairs. While the catalytic action mechanism of <em>Af</em>ogg protein is likely similar to the human Ogg1 (<em>hOgg</em><span>1), the DNA recognition mechanism and the basis for 8-oxoG substrate specificity of </span><em>Af</em>ogg differ from that of <em>hOgg</em>.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 99-111"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00081-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deletion of the SRS2 gene suppresses elevated recombination and DNA damage sensitivity in rad5 and rad18 mutants of Saccharomyces cerevisiae","authors":"Anna A Friedl ,&nbsp;Batia Liefshitz ,&nbsp;Rivka Steinlauf ,&nbsp;Martin Kupiec","doi":"10.1016/S0921-8777(01)00086-6","DOIUrl":"10.1016/S0921-8777(01)00086-6","url":null,"abstract":"<div><p>The <em>Saccharomyces</em> <em>cerevisiae</em> genes <em>RAD5</em>, <em>RAD18</em>, and <em>SRS2</em> are proposed to act in post-replicational repair of DNA damage. We have investigated the genetic interactions between mutations in these genes with respect to cell survival and ectopic gene conversion following treatment of logarithmic and early stationary cells with UV- and γ-rays. We find that the genetic interaction between the <em>rad5</em> and <em>rad18</em> mutations depends on DNA damage type and position in the cell cycle at the time of treatment. Inactivation of <em>SRS2</em> suppresses damage sensitivity both in <em>rad5</em> and <em>rad18</em> mutants, but only when treated in logarithmic phase. When irradiated in stationary phase, the <em>srs2</em> mutation enhances the sensitivity of <em>rad5</em> mutants, whereas it has no effect on <em>rad18</em> mutants. Irrespective of the growth phase, the <em>srs2</em> mutation reduces the frequency of damage-induced ectopic gene conversion in <em>rad5</em> and <em>rad18</em> mutants. In addition, we find that <em>srs2</em><span> mutants exhibit reduced spontaneous and UV-induced sister chromatid recombination (SCR), whereas </span><em>rad5</em> and <em>rad18</em> mutants are proficient for SCR. We propose a model in which the Srs2 protein has pro-recombinogenic or anti-recombinogenic activity, depending on the context of the DNA damage.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 137-146"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00086-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179962","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Effects of low iron conditions on the repair of DNA lesions induced by Cumene hydroperoxide in Escherichia coli cells” ☆: [Mutation Res. 485 (2001) 339–344]","authors":"L. Asad, D. C. Medeiros, I. Felzenszwalb, Á. Leitão, N. R. Asad","doi":"10.1016/S0921-8777(01)00094-5","DOIUrl":"https://doi.org/10.1016/S0921-8777(01)00094-5","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"30 1","pages":"165-166"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83864669","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nucleotide excision repair gene expression in the rat conceptus during organogenesis","authors":"Robert K. Vinson,&nbsp;Barbara F. Hales","doi":"10.1016/S0921-8777(01)00087-8","DOIUrl":"10.1016/S0921-8777(01)00087-8","url":null,"abstract":"<div><p><span>DNA repair may be a determinant of the susceptibility of the conceptus to DNA damaging teratogens<span>. The nucleotide excision repair (NER) pathway repairs a substantial amount of chemically induced DNA damage. The goals of this study were to assess the coordinate expression of NER genes in the midorganogenesis-stage rat conceptus and determine the consequences of exposure to the genotoxic teratogen, 4-hydroperoxycyclophosphamide (4-OOHCPA), on NER gene expression. Most NER genes were expressed at low levels in both yolk sac and embryo on gestational day (GD) 10, with the exception of </span></span><em>XPD, XPE</em> and <em>PCNA</em>. No significant alterations in gene expression occurred between GDs 10 and 11; in the yolk sac <em>XPB</em> expression increased on GD12 compared to either GD10 or 11. In the embryo, <em>XPE</em> expression increased between GDs 10 and 12, while <span><em>hHR23B, XPB, </em><em>ERCC1</em></span><span><span><span>, and DNA polymerase ε expression increased on GD12 relative to both GDs 10 and 11. Contrary to gene expression data, XPB protein was found at high levels and XPD at low levels in GDs 10–12 embryos and yolk sacs. Mirroring gene expression, high levels of PCNA protein were found in both tissues; </span>XPA protein levels were minimal in yolk sac from GDs 10–12 but increased in the embryo from moderate on GD10 to high on GD12. Therefore, NER gene expression during </span>organogenesis<span> was regulated in a developmental stage- and tissue-specific manner. Exposure of the conceptus to a teratogen, 4-OOHCPA, induced malformations without affecting NER transcript levels. Thus, NER gene expression in the conceptus was unresponsive to regulation by DNA alkylation.</span></span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 113-123"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00087-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Heterocyclic amine induced apoptotic response in the human lymphoblastoid cell line TK6 is linked to mismatch repair status","authors":"Romain Duc,&nbsp;Phaik-Mooi Leong-Morgenthaler","doi":"10.1016/S0921-8777(01)00090-8","DOIUrl":"10.1016/S0921-8777(01)00090-8","url":null,"abstract":"<div><p>The human lymphoblastoid cell, TK6, exhibited a dose-dependent cytotoxic and apoptotic response following treatment with the food borne heterocyclic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-<em>b</em><span><span>]pyridine (PhIP). Augmentation of the p53 protein and increases in p21-WAF1 levels were also observed. Comparison of the survival by clonogenic assays and the </span>percentage of apoptotic cells (cells containing subG1 DNA or condensed nuclei) revealed that only 10–20% of the PhIP-induced cell death could be attributed to apoptosis that occurred in the first 24</span> <!-->h after treatment. MT1, a derivative of TK6 that contains mutations in both alleles of its <em>hMSH6</em><span> gene and is mismatch repair deficient, showed a decreased apoptotic response. A significant increase (</span><em>P</em>&lt;0.05) in apoptosis was observed in TK6 and not in MT1 following treatment with 2.5<!--> <!-->μg/ml PhIP. A five- to six-fold increase and less than a two-fold increase in the fraction of apoptotic cells were observed in TK6 and MT1, respectively. Treatment with 5<!--> <!-->μg/ml PhIP resulted in significant increases in apoptosis (<em>P</em>&lt;0.05) in TK6 and MT1. The percentages of apoptotic cells were, however, two- to three-fold higher in TK6 than in MT1. HCT116, a hMLH1 defective mismatch repair deficient colorectal carcinoma cell line, also exhibited lower PhIP-induced apoptosis than its mismatch repair proficient chromosome transfer cell line (HCT116+chr3) following PhIP treatment. These results show that PhIP-induced apoptosis is mediated through a mismatch repair dependent pathway. Accumulation of p53 in TK6 and MT1 were evident in samples taken 24<!--> <!-->h after PhIP treatment. Increases in p21-WAF1 were also observed in both cell lines confirming that the p53 was functional. The lower apoptotic response of MT1 but similar p53 accumulation in TK6 and MT1 suggest that the mismatch repair protein(s) are involved downstream of p53 or that PhIP-induced apoptosis is p53-independent.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 155-164"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00090-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spontaneous germline amplification and translocation of a transgene array","authors":"Margot Kearns ,&nbsp;Christine Morris ,&nbsp;Emma Whitelaw","doi":"10.1016/S0921-8777(01)00084-2","DOIUrl":"10.1016/S0921-8777(01)00084-2","url":null,"abstract":"<div><p><span>The majority of the mammalian genome is thought to be relatively stable throughout and between generations. There are no developmentally programmed gene amplifications as seen in lower eukaryotes and </span>prokaryotes<span><span>, however a number of unscheduled gene amplifications have been documented. Apart from expansion of trinucleotide repeats<span> and minisatellite DNA, which involve small DNA elements, other cases of gene or DNA amplifications in mammalian systems have been reported in tumor samples or permanent cell lines. The mechanisms underlying these amplifications remain unknown. Here, we report a spontaneous transgene amplification through the male </span></span>germline<span> which resulted in silencing of transgene expression. During routine screening one mouse, phenotypically negative for transgene expression, was found to have a transgene copy number much greater than that of the transgenic parent. Analysis of the transgene expansion revealed that the amplification in the new high copy transgenic line resulted in a copy number approximately 40–60 times the primary transgenic line copy number of 5–8 copies per haploid genome. Genetic breeding analysis suggested that this amplification was the result of insertion at only one integration site, that it was stable for at least two generations and that the site of insertion was different from the site at which the original 5–8 copy array had integrated. FISH analysis revealed that the new high copy array was on chromosome 7<span> F3/4 whereas the original low copy transgene array had been localised to chromosome 3E3. DNA methylation analysis revealed that the high copy transgene array was heavily methylated. The amplification of transgenes, although a rare event, may give insight into amplification of endogenous genes which can be associated with human disease.</span></span></span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 125-136"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00084-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular mechanisms of DNA mismatch repair","authors":"Peggy Hsieh","doi":"10.1016/S0921-8777(01)00088-X","DOIUrl":"10.1016/S0921-8777(01)00088-X","url":null,"abstract":"<div><p><span><span>DNA mismatch repair (MMR) safeguards the integrity of the genome. In its role in postreplicative repair, this repair pathway corrects base–base and insertion/deletion (I/D) mismatches that have escaped the proofreading function of replicative </span>polymerases. In its absence, cells assume a mutator phenotype in which the rate of </span>spontaneous mutation is greatly elevated. The discovery that defects in mismatch repair segregate with certain cancer predisposition syndromes highlights its essential role in mutation avoidance. Recently, three-dimensional structures of MutS, a key repair protein that recognizes mismatches, have been determined by X-ray crystallography. This article provides an overview of the structural features of MutS proteins and discusses how the structural data together with biochemical and genetic studies reveal new insights into the molecular mechanisms of mismatch repair.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 71-87"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00088-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum to “Effects of low iron conditions on the repair of DNA lesions induced by Cumene hydroperoxide in Escherichia coli cells”","authors":"L.M.B.O Asad ,&nbsp;D.C Medeiros ,&nbsp;I Felzenszwalb ,&nbsp;A.C Leitão ,&nbsp;N.R Asad","doi":"10.1016/S0921-8777(01)00094-5","DOIUrl":"https://doi.org/10.1016/S0921-8777(01)00094-5","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 165-166"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00094-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72073186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translesion synthesis by the UmuC family of DNA polymerases","authors":"Zhigang Wang","doi":"10.1016/S0921-8777(01)00089-1","DOIUrl":"10.1016/S0921-8777(01)00089-1","url":null,"abstract":"<div><p>Translesion synthesis is an important cellular mechanism to overcome replication blockage by DNA damage. To copy damaged DNA templates during replication, specialized DNA polymerases are required. Translesion synthesis can be error-free or error-prone. From <em>E. coli</em><span><span> to humans, error-prone translesion synthesis constitutes a major mechanism of DNA damage-induced mutagenesis. As a </span>response to DNA damage during replication, translesion synthesis contributes to cell survival and induced mutagenesis. During 1999–2000, the UmuC superfamily had emerged, which consists of the following prototypic members: the </span><em>E. coli</em> UmuC, the <em>E. coli</em><span> DinB, the yeast Rad30, the human RAD30B, and the yeast Rev1. The corresponding biochemical activities are DNA polymerases V<span>, IV, η, ι, and dCMP transferase<span>, respectively. Recent studies of the UmuC superfamily are summarized and evidence is presented suggesting that this family of DNA polymerases is involved in translesion DNA synthesis.</span></span></span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 59-70"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00089-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The p48 subunit of the damaged-DNA binding protein DDB associates with the CBP/p300 family of histone acetyltransferase","authors":"Abhishek Datta ,&nbsp;Srilata Bagchi ,&nbsp;Alo Nag ,&nbsp;Pavel Shiyanov ,&nbsp;Guy R Adami ,&nbsp;Taewon Yoon ,&nbsp;Pradip Raychaudhuri","doi":"10.1016/S0921-8777(01)00082-9","DOIUrl":"10.1016/S0921-8777(01)00082-9","url":null,"abstract":"<div><p><span><span>DDB has been implicated in DNA repair as well as transcription. Mutations in DDB have been correlated with the repair-deficiency disease, xeroderma pigmentosum group E (XP-E). The XP-E cells exhibit deficiencies in global genomic repair, suggesting a role for DDB in that process. DDB also possesses a transcription stimulatory activity. We showed that DDB could function as a transcriptional partner of </span>E2F1<span>. But the mechanism by which DDB stimulates E2F-regulated transcription or carry out its DNA repair function is not understood. To investigate the mechanisms, we looked for nuclear proteins that interact with DDB. Here we show that DDB associates with the CBP/p300 family of proteins, in vivo and in vitro. We suggest that DDB participates in global genomic repair by recruiting CBP/p300 to the damaged-chromatin. It is possible that the </span></span>histone acetyltransferase<span> activities of the CBP/p300 proteins induce chromatin remodeling at the damaged-sites to allow recruitment of the repair complexes. The observation offers insights into both transcription and repair functions of DDB.</span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"486 2","pages":"Pages 89-97"},"PeriodicalIF":0.0,"publicationDate":"2001-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00082-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56179935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}