Enzymatic switching for efficient and accurate translesion DNA replication

Scott D. McCulloch, Robert J. Kokoska, Olga Chilkova, Carrie M. Welch, Erik Johansson, Peter M.J. Burgers, Thomas A. Kunkel

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When cyclobutane pyrimidine dimers stall DNA replication by DNA polymerase (Pol) δ or E, a switch occurs to allow translesion synthesis by DNA polymerase η, followed by another switch that allows normal replication to resume. In the present study, we investigate these switches using Saccharomyces cerevisiae Pol δ, Pol E and Pol η and a series of matched and mismatched primer templates that mimic each incorporation needed to completely bypass a cis-syn thymine-thymine (TT) dimer. We report a complementary pattern of substrate use indicating that enzymatic switching involving localized translesion synthesis by Pol η and mismatch excision and polymerization by a major replicative polymerase can account for the efficient and accurate dimer bypass known to suppress sunlight-induced mutagenesis and skin cancer.

Original languageEnglish
Pages (from-to)4665-4675
Number of pages11
JournalNucleic acids research
Issue number15
StatePublished - Oct 15 2004

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    McCulloch, S. D., Kokoska, R. J., Chilkova, O., Welch, C. M., Johansson, E., Burgers, P. M. J., & Kunkel, T. A. (2004). Enzymatic switching for efficient and accurate translesion DNA replication. Nucleic acids research, 32(15), 4665-4675. https://doi.org/10.1093/nar/gkh777