Mutation Research/DNA Repair最新文献

{"title":"S. cerevisiae has three pathways for DNA interstrand crosslink repair","authors":"Kenneth F Grossmann,&nbsp;Alex M Ward,&nbsp;Mara E Matkovic,&nbsp;Alexandra E Folias,&nbsp;Robb E Moses","doi":"10.1016/S0921-8777(01)00106-9","DOIUrl":"10.1016/S0921-8777(01)00106-9","url":null,"abstract":"<div><p>Yeast mutants, <em>snm1 (pso2-1)</em>, <em>rev3 (pso1-1)</em>, and <em>rad51</em>, which display significant sensitivity to interstrand crosslinks (ICLs) have low relative sensitivity to other DNA damaging agents. <em>SNM1</em>, <em>REV3</em>, and <span><em>RAD51</em></span> were disrupted in the same haploid strain, singly and in combination. The double mutants, <em>snm1Δ rev3Δ</em>, <em>snm1Δ rad51Δ</em> and <em>rev3Δ rad51Δ</em><span> were all more sensitive to ICLs than any of the single mutants, indicating that they are in separate epistasis groups for survival. A triple mutant displayed greater sensitivity to ICLs than any of the double mutants, with one ICL per genome being lethal. Therefore, </span><span><em>Saccharomyces cerevisiae</em></span><span> appears to have three separate ICL repair pathways, but no more. S-phase delay was not observed after ICL damage introduced by cisplatin (CDDP) or 8-methoxypsoralen (8-MOP) during the G1-phase, in any of the above mutants, or in an isogenic </span><em>rad14Δ</em><span> mutant deficient in nucleotide excision repair. However, the psoralen analog angelicin (monoadduct damage) induced a significant S-phase delay in the </span><em>rad14Δ</em> mutant. Thus, normal S-phase in the presence of ICLs does not seem to be due to rapid excision repair. The results also indicate that monoadduct formation by CDDP or 8-MOP at the doses used is not sufficient to delay S-phase in the <em>rad14Δ</em> mutant. While the sensitivity of a <em>rev3Δ</em> mutant indicates Polζ is needed for optimal ICL repair, isogenic cells deficient in Polη (<em>rad30Δ</em> cells) were not significantly more sensitive to ICL agents than wild-type cells, and have no S-phase delay.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 73-83"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00106-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180248","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":"CUMULATIVE KEYWORD INDEX 2001","authors":"","doi":"10.1016/S0921-8777(01)00120-3","DOIUrl":"https://doi.org/10.1016/S0921-8777(01)00120-3","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 199-201"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00120-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72064798","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":"Disruption of Xpg increases spontaneous mutation frequency, particularly A:T to C:G transversion","authors":"Naoko Shiomi ,&nbsp;Emiko Hayashi ,&nbsp;Shun-ichi Sasanuma ,&nbsp;Kazuei Mita ,&nbsp;Tadahiro Shiomi","doi":"10.1016/S0921-8777(01)00111-2","DOIUrl":"10.1016/S0921-8777(01)00111-2","url":null,"abstract":"<div><p>Cells isolated from <em>Xpg</em> (the mouse counterpart of XPG)-disrupted mice underwent premature senescence and showed early onset of immortalization, suggesting that <em>Xpg</em><span><span> might be involved in genetic stability. Recent studies showed that human XPG, in addition to its function in the nucleotide excision repair (NER), was involved in the repair of oxidative base damages such as </span>thymine glycol (Tg) and 8-oxo-guanine (8-oxoG), and this may explain the genetic instability observed in </span><em>Xpg</em><span>-deficient cells. To clarify this point, we determined spontaneous mutation<span> frequencies and the type of spontaneous base substitution mutations in cells obtained from normal and </span></span><em>Xpg</em>-deficient mice using the <em>supF</em><span> shuttle vector (pNY200) for mutation assay. The spontaneous mutation frequency of the </span><em>supF</em> gene in pNY200 propagated in the <em>Xpg</em>-deficient cells was about three times higher than that in normal cells, indicating the importance of <em>Xpg</em><span> in reducing the frequency of spontaneous mutations. The frequency of spontaneous base substitution mutations at A:T sites, particularly that of the A:T to C:G transversion, increased markedly in the </span><em>Xpg</em>-deficient cells.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 127-135"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00111-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180308","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":"CUMULATIVE AUTHOR INDEX FOR 2001","authors":"","doi":"10.1016/S0921-8777(01)00119-7","DOIUrl":"https://doi.org/10.1016/S0921-8777(01)00119-7","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 193-197"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00119-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72064799","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 characterization of ionizing radiation-hypersensitive mutant M10 cells","authors":"Masahiko Mori ,&nbsp;Hiromi Itsukaichi ,&nbsp;Atsuko Nakamura ,&nbsp;Koki Sato","doi":"10.1016/S0921-8777(01)00107-0","DOIUrl":"10.1016/S0921-8777(01)00107-0","url":null,"abstract":"<div><p>An ionizing radiation-sensitive mutant derivative of mouse lymphoma L5178Y cell, M10, is defective in rejoining DNA double-strand breaks (DSBs). The complementation test and the results of chromosome transfer suggested that M10 may belong to X-ray cross-complementation (XRCC) group 4. In the present study, sequence analysis of <em>Xrcc4</em><span> cDNA in M10 cells disclosed a transversion of A (370) to T, which results in a change of arginine (124) to a termination codon. Interestingly, the mutation occurred in one allele and the transcripts of the </span><em>Xrcc4</em> gene were expressed exclusively from the mutant allele. Transfection of M10 cells with the murine <em>Xrcc4</em><span> cDNA completely rescued X-ray sensitivity of the mutant cells. M10 is a novel </span><em>Xrcc4</em>-deficient cell line.</p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 85-92"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00107-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180262","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":"A new assay to quantify in vivo repair of G:T mispairs by base excision repair","authors":"Stephen B Waters,&nbsp;Steven A Akman","doi":"10.1016/S0921-8777(01)00112-4","DOIUrl":"10.1016/S0921-8777(01)00112-4","url":null,"abstract":"<div><p><span><span>The double mismatch reversion (DMR) assay quantifies the repair of G:T mispairs exclusively by base excision repair in vivo. Synthetic </span>oligonucleotides containing two G:T mispairs on opposite strands were placed into the suppressor tRNA gene </span><em>supF</em> in the shuttle plasmid pDMR. Placement of two mispairs on opposite strands of <em>supF</em> creates a one to one correspondence between the number of correct repair events prior to replication in which G:T mispairs are converted to G:C base pairs and the number of post-replication progeny plasmids with functional <em>supF</em>. Replication of unrepaired or incorrectly repaired mispairs cannot produce progeny plasmids containing functional <em>supF</em>. Indeed, direct transformation of <em>Escherichia</em> <em>coli</em> strain MBL50, which reports the functional status of <em>supF</em>, with pDMR constructs containing two G:T or G:G mispairs yielded &lt;0.5% wild-type <em>supF</em>-containing colonies. In contrast, passage of G:T mispair-containing pDMR constructs through human 5637 bladder carcinoma cells for 48<!--> <!-->h prior to plasmid recovery and transformation of the reporter <em>E.</em> <em>coli</em> strain MBL50 produced 47% wild-type <em>supF</em>-containing colonies. This finding was indicative of repair prior to the onset of replication in 5637 cells. However, passage of G:G mispair-containing pDMR constructs through 5637 cells yielded &lt;0.5% wild-type <em>supF</em><span>-containing colonies. Moreover, no difference was observed in the rate of G:T mispair repair by HCT 116 colorectal carcinoma cells deficient in long-patch mismatch repair and a long-patch mismatch repair proficient HCT 116 subline. These data demonstrate that repair measured by the DMR assay is exclusively attributable to short-patch pathways. The DMR assay proved useful in the analysis of the effect of the base 5′ to a mispaired G on the rate of G:T base excision repair by 5637 cells, indicating the sequence preference CpG≈5mCpG&gt;TpG&gt;GpG≈ApG, and in the comparison of G:T base excision repair rates between cell lines.</span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 109-119"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00112-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180318","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":"CONTENTS TO VOLUME 487","authors":"","doi":"10.1016/S0921-8777(01)00118-5","DOIUrl":"https://doi.org/10.1016/S0921-8777(01)00118-5","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 191-192"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00118-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72064800","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 MAG1 DNA glycosylase gene suppresses alkylation-induced killing and mutagenesis in yeast cells lacking AP endonucleases","authors":"Wei Xiao ,&nbsp;Barbara L Chow ,&nbsp;Michelle Hanna ,&nbsp;Paul W Doetsch","doi":"10.1016/S0921-8777(01)00113-6","DOIUrl":"10.1016/S0921-8777(01)00113-6","url":null,"abstract":"<div><p><span>DNA base excision repair<span><span> (BER) is initiated by DNA glycosylases that recognize and remove damaged bases. The phosphate backbone adjacent to the resulting apurinic/apyrimidinic (AP) site is then cleaved by an AP endonuclease or glycosylase-associated AP </span>lyase to invoke subsequent BER steps. We have used a genetic approach in </span></span><span><em>Saccharomyces cerevisiae</em></span> to address whether AP sites are blocks to DNA replication and the biological consequences if AP sites persist in the genome. We found that yeast cells deficient in the two AP endonucleases (<em>apn1 apn2</em><span> double mutant) are extremely sensitive to killing by methyl methanesulfonate (MMS), a model DNA alkylating agent. Interestingly, this sensitivity can be reduced up to 2500-fold by deleting the </span><span><em>MAG1</em></span><span><span> 3-methyladenine DNA glycosylase gene, suggesting that Mag1 not only removes lethal base lesions, but also benign lesions and possibly normal bases, and that the resulting AP sites are highly toxic to the cells. This rescuing effect appears to be specific for DNA </span>alkylation damage, since the </span><em>mag1</em> mutation reduces killing effects of two other DNA alkylating agents, but does not alter the sensitivity of <em>apn</em> cells to killing by UV, γ-ray or H₂O₂<span>. Our mutagenesis assays indicate that nearly half of spontaneous and almost all MMS-induced mutations in the AP endonuclease-deficient cells are due to Mag1 DNA glycosylase activity. Although the DNA replication apparatus appears to be incapable of replicating past AP sites, Polζ-mediated translesion synthesis is able to bypass AP sites, and accounts for all spontaneous and MMS-induced mutagenesis in the AP endonuclease-deficient cells. These results allow us to delineate base lesion flow within the BER pathway and link AP sites to other DNA damage repair and tolerance pathways.</span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 137-147"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00113-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180334","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":"Relationship between base excision repair capacity and DNA alkylating agent sensitivity in mouse monocytes","authors":"Kuang-Hua Chen ,&nbsp;Deepak K. Srivastava ,&nbsp;Samuel H. Wilson","doi":"10.1016/S0921-8777(01)00110-0","DOIUrl":"10.1016/S0921-8777(01)00110-0","url":null,"abstract":"<div><p><span><span>Base excision repair (BER) capacity and the level of </span>DNA polymerase β (β-pol) are higher in mouse </span>monocyte<span> cell extracts when cells are treated with oxidative stress-inducing agents. Consistent with this, such treated cells are more resistant to the cytotoxic effects of methyl methanesulfonate (MMS), which produces DNA damage considered to be repaired by the BER pathway. In contrast to the up-regulation of BER in oxidatively stressed cells, cells treated with the cytokine interferon-γ (IFN-γ) are down-regulated in both BER capacity of the cell extract and level of β-pol. We find that cells treated with IFN-γ are more sensitive to MMS than untreated cells. These results demonstrate concordance between β-pol level, BER capacity and cellular sensitivity to a DNA methylation-inducing agent. The results suggest that BER is a significant defense mechanism in mouse monocytes against the cytotoxic effects of methylated DNA.</span></p></div>","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Pages 121-126"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00110-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56180298","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":"Publishers note","authors":"","doi":"10.1016/S0921-8777(01)00117-3","DOIUrl":"https://doi.org/10.1016/S0921-8777(01)00117-3","url":null,"abstract":"","PeriodicalId":100935,"journal":{"name":"Mutation Research/DNA Repair","volume":"487 3","pages":"Page v"},"PeriodicalIF":0.0,"publicationDate":"2001-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0921-8777(01)00117-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72064818","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}