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

Melike Çağlayan () and Samuel H. Wilson ()
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Melike Çağlayan: Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences
Samuel H. Wilson: Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences

Nature Communications, 2018, vol. 9, issue 1, 1-4

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-06700-5

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