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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
Subject categories Functional genomics, Molecular biology, Molecular biology, Genetics, Bioinformatics and Systems Biology, Cell and Molecular Biology


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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