| Mutations arising during repair of chromosome breaks. | |
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MedLine Citation:
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PMID: 23146099 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Mutations stimulate evolutionary change and lead to birth defects and cancer in humans as well as to antibiotic resistance in bacteria. According to the classic view, most mutations arise in dividing cells and result from uncorrected errors of S-phase DNA replication, which is highly accurate because of the involvement of selective DNA polymerases and efficient error-correcting mechanisms. In contrast, studies in bacteria and yeast reveal that DNA synthesis associated with repair of double-strand chromosomal breaks (DSBs) by homologous recombination is highly inaccurate, thus making DSBs and their repair an important source of mutations. Different error-prone mechanisms appear to operate in different repair scenarios. In the filling in of single-stranded DNA regions, error-prone translesion DNA polymerases appear to produce most errors. In contrast, in gene conversion gap repair and in break-induced replication, errors are independent of translesion polymerases, and many mutations have the signatures of template switching during DNA repair synthesis. DNA repair also appears to create complex copy-number variants. Overall, homologous recombination, which is traditionally considered a safe pathway of DSB repair, is an important source of mutagenesis that may contribute to human disease and evolution. |
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Authors:
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Anna Malkova; James E Haber |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: Annual review of genetics Volume: 46 ISSN: 1545-2948 ISO Abbreviation: Annu. Rev. Genet. Publication Date: 2012 |
Date Detail:
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Created Date: 2012-11-13 Completed Date: 2013-04-22 Revised Date: 2013-05-09 |
Medline Journal Info:
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Nlm Unique ID: 0117605 Medline TA: Annu Rev Genet Country: United States |
Other Details:
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Languages: eng Pagination: 455-73 Citation Subset: IM |
Affiliation:
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Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202-5132, USA. amalkova@iupui.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adaptation, Biological Chromosome Breakage* Chromosomes, Bacterial / genetics* Chromosomes, Fungal / genetics Crossing Over, Genetic DNA Breaks, Double-Stranded* DNA Copy Number Variations DNA Repair* DNA Replication* DNA, Bacterial / genetics DNA, Fungal / genetics Escherichia coli / genetics Mutagenesis Mutation* Saccharomycetales / genetics |
| Grant Support | |
ID/Acronym/Agency:
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GM084242/GM/NIGMS NIH HHS; GM20056/GM/NIGMS NIH HHS; GM61766/GM/NIGMS NIH HHS; GM76020/GM/NIGMS NIH HHS; R01 GM076020/GM/NIGMS NIH HHS; R37 GM020056/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Bacterial; 0/DNA, Fungal |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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