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

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  • Melike Çağlayan

    (Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences
    University of Florida)

  • Samuel H. Wilson

    (Genome Integrity and Structural Biology Laboratory, National Institutes of Health, National Institute of Environmental Health Sciences)

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.

Suggested Citation

  • Melike Çağlayan & Samuel H. Wilson, 2018. "Pol μ dGTP mismatch insertion opposite T coupled with ligation reveals promutagenic DNA repair intermediate," Nature Communications, Nature, vol. 9(1), pages 1-4, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06700-5
    DOI: 10.1038/s41467-018-06700-5
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    Cited by:

    1. Qun Tang & Mitchell Gulkis & Robert McKenna & Melike Çağlayan, 2022. "Structures of LIG1 that engage with mutagenic mismatches inserted by polβ in base excision repair," Nature Communications, Nature, vol. 13(1), pages 1-11, December.

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