Work

Enzymatic switching for efficient and accurate translesion DNA replication

Year: 2004

Type: article

Abstract: When cyclobutane pyrimidine dimers stall DNA replication by DNA polymerase (Pol) delta or epsilon, a switch occurs to allow translesion synthesis by DNA polymerase eta, followed by another switch that allows normal replication to resume. In the present study, we investigate these switches using Saccharomyces cerevisiae Pol delta, Pol epsilon and Pol eta 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 eta 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.

Source: Nucleic Acids Research

DOI: 10.1093/nar/gkh777

Author: S. D. McCulloch

Institutions: National Institutes of Health, National Institute of Environmental Health Sciences

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funders: Cancerfonden, Vetenskapsrådet, National Institutes of Health, National Institute of General Medical Sciences

Awards: STRUCTURE/FUNCTION OF YEAST DNA POLYMERASE DELTA, G5542748776, ENZYMOLOGY OF REPLICATION OF YEAST CHROMOSOMAL DNA