DNA polymerase η contributes to genome-wide lagging strand synthesis
Journal article, 2019

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.

Author

Katrin Kreisel

University of Gothenburg

Martin Engqvist

University of Gothenburg

Chalmers, Biology and Biological Engineering, Systems and Synthetic Biology

Josephine Kalm

University of Gothenburg

Liam J. Thompson

University of Gothenburg

Martin Boström

University of Gothenburg

Clara Navarrete Roman

University of Gothenburg

John P. McDonald

National Institute of Child Health and Human Development

Erik Larsson

University of Gothenburg

Roger Woodgate

National Institute of Child Health and Human Development

Anders R. Clausen

University of Gothenburg

Nucleic Acids Research

0305-1048 (ISSN) 1362-4962 (eISSN)

Vol. 47 5 2425-2435

Subject Categories

Medical Bioscience

Biochemistry and Molecular Biology

Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)

DOI

10.1093/nar/gky1291

PubMed

30597049

More information

Latest update

5/27/2019