Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis.

ABSTRACT: Polymerase eta (PolH) is necessary for translesion DNA synthesis, and PolH deficiency predisposes xeroderma pigmentosum variant (XPV) patients to cancer. Due to the critical role of PolH in translesion DNA synthesis, the activity of PolH is tightly controlled and subjected to multiple regulations, especially posttranslational modifications. Here, we show that PolH-dependent lesion bypass and intracellular translocation are regulated by Pirh2 E3 ubiquitin ligase through monoubiquitination. Specifically, we show that Pirh2, a target of the p53 tumor suppressor, monoubiquitinates PolH at one of multiple lysine residues. We also show that monoubiquitination of PolH inhibits the ability of PolH to interact with PCNA and to bypass UV-induced lesions, leading to decreased viability of UV-damaged

SUBMITTER: Jung YS 

PROVIDER: S-EPMC3187371 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature