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Nat Commun. 2018 Oct 11;9(1):4213. doi: 10.1038/s41467-018-06700-5.

Pol μ dGTP mismatch insertion opposite T coupled with ligation reveals promutagenic DNA repair intermediate.

Author information

1
Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA. caglayanm@ufl.edu.
2
Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL, 32610, USA. caglayanm@ufl.edu.
3
Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences, Research Triangle Park, NC, 27709, USA. wilson5@niehs.nih.gov.

Abstract

Incorporation of mismatched nucleotides during DNA replication or repair leads to transition or transversion mutations and is considered as a predominant source of base substitution mutagenesis in cancer cells. Watson-Crick like dG:dT base pairing is considered to be an important source of genome instability. Here we show that DNA polymerase (pol) μ insertion of 7,8-dihydro-8'-oxo-dGTP (8-oxodGTP) or deoxyguanosine triphosphate (dGTP) into a model double-strand break DNA repair substrate with template base T results in efficient ligation by DNA ligase. These results indicate that pol μ-mediated dGTP mismatch insertion opposite template base T coupled with ligation could be a feature of mutation prone nonhomologous end joining during double-strand break repair.

PMID:
30310068
PMCID:
PMC6181931
DOI:
10.1038/s41467-018-06700-5
[Indexed for MEDLINE]
Free PMC Article

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