A non-catalytic role of DNA polymerase eta in recruiting Rad18 and promoting PCNA monoubiquitination at stalled replication forks

作者：Durando Michael^*; Tateishi Satoshi; Vaziri Cyrus

来源：Nucleic Acids Research, 2013, 41(5): 3079-3093.

DOI：10.1093/nar/gkt016

Trans-lesion DNA synthesis (TLS) is a DNA damage-tolerance mechanism that uses low-fidelity DNA polymerases to replicate damaged DNA. The inherited cancer-propensity syndrome xeroderma pigmentosum variant (XPV) results from error-prone TLS of UV-damaged DNA. TLS is initiated when the Rad6/Rad18 complex monoubiquitinates proliferating cell nuclear antigen (PCNA), but the basis for recruitment of Rad18 to PCNA is not completely understood. Here, we show that Rad18 is targeted to PCNA by DNA polymerase eta (Pol eta), the XPV gene product that is mutated in XPV patients. The C-terminal domain of Pol eta binds to both Rad18 and PCNA and promotes PCNA monoubiquitination, a function unique to Pol eta among Y-family TLS polymerases and dissociable from its catalytic activity. Importantly, XPV cells expressing full-length catalytically-inactive Pol eta exhibit increased recruitment of other error-prone TLS polymerases (Pol kappa and Pol iota) after UV irradiation. These results define a novel non-catalytic role for Pol eta in promoting PCNA monoubiquitination and provide a new potential mechanism for mutagenesis and genome instability in XPV individuals.

• 出版日期2013-3