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dc.contributor.authorWyrzykowski, Jennifer
dc.contributor.authorVolkert, Michael R.
dc.date2022-08-11T08:10:03.000
dc.date.accessioned2022-08-23T16:53:30Z
dc.date.available2022-08-23T16:53:30Z
dc.date.issued2003-02-20
dc.date.submitted2008-08-04
dc.identifier.citation<p>J Bacteriol. 2003 Mar;185(5):1701-4.</p>
dc.identifier.issn0021-9193 (Print)
dc.identifier.pmid12591888
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42290
dc.description.abstractA major role of the methyl-directed mismatch repair (MMR) system of Escherichia coli is to repair postreplicative errors. In this report, we provide evidence that MMR also acts on oxidized DNA, preventing mutagenesis. When cells deficient in MMR are grown anaerobically, spontaneous mutation frequencies are reduced compared with those of the same cells grown aerobically. In addition, we show that a dam mutant has an increased sensitivity to hydrogen peroxide treatment that can be suppressed by mutations that inactivate MMR. In a dam mutant, MMR is not targeted to newly replicated DNA strands and therefore mismatches are converted to single- and double-strand DNA breaks. Thus, base pairs containing oxidized bases will be converted to strand breaks if they are repaired by MMR. This is demonstrated by the increased peroxide sensitivity of a dam mutant and the finding that the sensitivity can be suppressed by mutations inactivating MMR. We demonstrate further that this repair activity results from MMR recognition of base pairs containing 8-oxoguanine (8-oxoG) based on the finding that overexpression of the MutM oxidative repair protein, which repairs 8-oxoG, can suppress the mutH-dependent increase in transversion mutations. These findings demonstrate that MMR has the ability to prevent oxidative mutagenesis either by removing 8-oxoG directly or by removing adenine misincorporated opposite 8-oxoG or both.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=12591888&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC148063/
dc.subjectAnaerobiosis
dc.subject*Base Pair Mismatch
dc.subjectCell Division
dc.subjectDNA
dc.subjectDNA Damage
dc.subject*DNA Repair
dc.subject*DNA Repair Enzymes
dc.subjectDNA, Single-Stranded
dc.subjectDNA-Binding Proteins
dc.subjectDNA-Formamidopyrimidine Glycosylase
dc.subjectEndodeoxyribonucleases
dc.subjectEscherichia coli
dc.subject*Escherichia coli Proteins
dc.subjectGene Expression Regulation
dc.subjectGuanine
dc.subjectHydrogen Peroxide
dc.subjectMutation
dc.subjectN-Glycosyl Hydrolases
dc.subjectOxidation-Reduction
dc.subjectOxidative Stress
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleThe Escherichia coli methyl-directed mismatch repair system repairs base pairs containing oxidative lesions
dc.typeJournal Article
dc.source.journaltitleJournal of bacteriology
dc.source.volume185
dc.source.issue5
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/653
dc.identifier.contextkey564461
html.description.abstract<p>A major role of the methyl-directed mismatch repair (MMR) system of Escherichia coli is to repair postreplicative errors. In this report, we provide evidence that MMR also acts on oxidized DNA, preventing mutagenesis. When cells deficient in MMR are grown anaerobically, spontaneous mutation frequencies are reduced compared with those of the same cells grown aerobically. In addition, we show that a dam mutant has an increased sensitivity to hydrogen peroxide treatment that can be suppressed by mutations that inactivate MMR. In a dam mutant, MMR is not targeted to newly replicated DNA strands and therefore mismatches are converted to single- and double-strand DNA breaks. Thus, base pairs containing oxidized bases will be converted to strand breaks if they are repaired by MMR. This is demonstrated by the increased peroxide sensitivity of a dam mutant and the finding that the sensitivity can be suppressed by mutations inactivating MMR. We demonstrate further that this repair activity results from MMR recognition of base pairs containing 8-oxoguanine (8-oxoG) based on the finding that overexpression of the MutM oxidative repair protein, which repairs 8-oxoG, can suppress the mutH-dependent increase in transversion mutations. These findings demonstrate that MMR has the ability to prevent oxidative mutagenesis either by removing 8-oxoG directly or by removing adenine misincorporated opposite 8-oxoG or both.</p>
dc.identifier.submissionpathoapubs/653
dc.contributor.departmentDepartment of Molecular Genetics and Microbiology
dc.source.pages1701-4


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