Journal article
Mutations arising during repair of chromosome breaks
Annual review of genetics, Vol.46(1), pp.455-473
2012
DOI: 10.1146/annurev-genet-110711-155547
PMID: 23146099
Abstract
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.
Details
- Title: Subtitle
- Mutations arising during repair of chromosome breaks
- Creators
- Anna Malkova - Department of Biology, School of Science, IUPUI, Indianapolis, Indiana 46202-5132, USA. amalkova@iupui.eduJames E Haber
- Resource Type
- Journal article
- Publication Details
- Annual review of genetics, Vol.46(1), pp.455-473
- DOI
- 10.1146/annurev-genet-110711-155547
- PMID
- 23146099
- ISSN
- 0066-4197
- eISSN
- 1545-2948
- Grant note
- GM61766 / NIGMS NIH HHS GM20056 / NIGMS NIH HHS GM084242 / NIGMS NIH HHS R01 GM084242 / NIGMS NIH HHS R01 GM076020 / NIGMS NIH HHS R37 GM020056 / NIGMS NIH HHS GM76020 / NIGMS NIH HHS
- Language
- English
- Date published
- 2012
- Academic Unit
- Biology
- Record Identifier
- 9984217534002771
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