DNA polymerase η contributes to genome-wide lagging strand synthesis
Artikel i vetenskaplig tidskrift, 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.
Författare
Katrin Kreisel
Göteborgs universitet
Martin Engqvist
Göteborgs universitet
Chalmers, Biologi och bioteknik, Systembiologi
Josephine Kalm
Göteborgs universitet
Liam J. Thompson
Göteborgs universitet
Martin Boström
Göteborgs universitet
Clara Navarrete Roman
Göteborgs universitet
John P. McDonald
National Institute of Child Health and Human Development
Erik Larsson
Göteborgs universitet
Roger Woodgate
National Institute of Child Health and Human Development
Anders R. Clausen
Göteborgs universitet
Nucleic Acids Research
0305-1048 (ISSN) 1362-4962 (eISSN)
Vol. 47 5 2425-2435Ämneskategorier
Medicinsk biovetenskap
Biokemi och molekylärbiologi
Medicinsk bioteknologi (med inriktning mot cellbiologi (inklusive stamcellsbiologi), molekylärbiologi, mikrobiologi, biokemi eller biofarmaci)
DOI
10.1093/nar/gky1291
PubMed
30597049