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 2425-2435Subject 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