Enzymatic switching for efficient and accurate translesion DNA replication |
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| Authors: | McCulloch Scott D Kokoska Robert J Chilkova Olga Welch Carrie M Johansson Erik Burgers Peter M J Kunkel Thomas A |
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| Affiliation: | Laboratory of Molecular Genetics and Laboratory of Structural Biology, National Institute of Environmental Health Sciences, NIH, DHHS, Research Triangle Park, NC 27709, USA. |
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| Abstract: | When cyclobutane pyrimidine dimers stall DNA replication by DNA polymerase (Pol) δ or ε, 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 ε 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. |
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