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

Research output: Contribution to journalArticle

73 Scopus citations

Abstract

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
Volume32
Issue number15
DOIs
StatePublished - Oct 15 2004

Fingerprint Dive into the research topics of 'Enzymatic switching for efficient and accurate translesion DNA replication'. Together they form a unique fingerprint.

  • Cite this

    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