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DNA polymerase η contributes to genome-wide lagging strand synthesis.

Journal article
Authors Katrin Kreisel
Martin K M Engqvist
Josephine Kalm
Liam J. Thompson
Martin Boström
Clara Navarrete
John P McDonald
Erik Larsson
Roger Woodgate
Anders R Clausen
Published in Nucleic acids research
Volume 47
Issue 5
Pages 2425–2435
ISSN 1362-4962
Publication year 2019
Published at Institute of Biomedicine, Department of Medical Biochemistry and Cell Biology
Pages 2425–2435
Language en
Links dx.doi.org/10.1093/nar/gky1291
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Functional genomics, Molecular biology, Molecular biology, Genetics, Bioinformatics and Systems Biology, Cell and Molecular Biology

Abstract

DNA polymerase η (pol η) is best known for its ability to bypass UV-induced thymine-thymine (T-T) dimers and other bulky DNA lesions, but pol η also has other cellular roles. Here, we present evidence that pol η competes with DNA polymerases α and δ for the synthesis of the lagging strand genome-wide, where it also shows a preference for T-T in the DNA template. Moreover, we found that the C-terminus of pol η, which contains a PCNA-Interacting Protein motif is required for pol η to function in lagging strand synthesis. Finally, we provide evidence that a pol η dependent signature is also found to be lagging strand specific in patients with skin cancer. Taken together, these findings provide insight into the physiological role of DNA synthesis by pol η and have implications for our understanding of how our genome is replicated to avoid mutagenesis, genome instability and cancer.

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