Human DNA polymerase η activity and translocation is regulated by phosphorylation (original) (raw)

2008, Proceedings of the National Academy of Sciences

Human DNA polymerase η (pol η) can replicate across UV-induced pyrimidine dimers, and defects in the gene encoding pol η result in a syndrome called xeroderma pigmentosum variant (XP-V). XP-V patients are prone to the development of cancer in sun-exposed areas, and cells derived from XP-V patients demonstrate increased sensitivity to UV radiation and a higher mutation rate compared with wild-type cells. pol η has been shown to replicate across a wide spectrum of DNA lesions introduced by environmental or chemotherapeutic agents, or during nucleotide starvation, suggesting that the biological roles for pol η are not limited to repair of UV-damaged DNA. The high error rate of pol η requires that its intracellular activity be tightly regulated. Here, we show that the phosphorylation of pol η increased after UV irradiation, and that treatment with caffeine, siRNA against ATR, or an inhibitor of PKC (calphostin C), reduced the accumulation of pol η at stalled replication forks after UV i...

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