Enzymatic switching for efficient and accurate translesion DNA replication

• Published in: Nucleic acids research 2004-01, Vol.32 (15), p.4665-4675
• Main Authors: McCulloch, S.D, Kokoska, R.J, Chilkova, O, Welch, C.M, Johansson, E, Burgers, P.M.J, Kunkel, T.A
• Format: Article
• Language: English
• Subjects: Base Pair Mismatch; DNA Damage; DNA Polymerase II - metabolism; DNA Polymerase III - metabolism; DNA repair; DNA Replication; DNA templates; DNA-directed DNA polymerase; DNA-Directed DNA Polymerase - metabolism; enzyme activity; Exodeoxyribonucleases - metabolism; Models, Genetic; Pyrimidine Dimers - metabolism; Saccharomyces cerevisiae; Saccharomyces cerevisiae - enzymology; thymine-thymine dimer bypass; yeasts
• ISSN: 0305-1048; 1362-4962; 1362-4962
• DOI: 10.1093/nar/gkh777

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.