Non-Recombinogenic Role for Rad52, Rad51 and Rad57 in Translesion Synthesis

Abstract

DNA damage tolerance relies on homologous recombination (HR) and translesion synthesis (TLS) mechanisms to fill in the ssDNA gaps generated during the replication fork bypass of blocking DNA lesions. Whereas TLS requires specialized polymerases able to incorporate a dNTP opposite the lesion and is error-prone, HR uses the sister chromatid to repair the ssDNA gap and is mostly error-free. We report that the HR proteins Rad52, Rad51 and Rad57 act in concert with the TLS machinery (Rad6/Rad18-mediated PCNA ubiquitylation and polymerases Rev1/Pol ζ) to repair ssDNA gaps through a non-recombinogenic function, and accordingly they are required for DNA damage-induced mutagenesis. Specifically, Rad52, Rad51 and Rad57, but not Rad54, facilitate Rad6/Rad18 binding to chromatin and subsequent DNA damage-induced PCNA ubiquitylation. In sum, Rad51, Rad52 and Rad57 drive the tolerance process to HR or TLS through recombinational and non-recombinational functions, providing a novel role for the recombination proteins in maintaining genome integrity.