DNA double-strand breaks (DSBs) constitute one of the most cytotoxic forms of DNA damage and pose a significant threat to cell viability, survival, and homeostasis. DSBs have the potential to promote aneuploidy, cell death and potentially deleterious mutations that promote tumorigenesis. Homologous recombination (HR) is one of the main DSB repair pathways and while being essential for cell survival under genotoxic stress, it requires proper regulation to avoid chromosome rearrangements. Here, we characterize the Saccharomyces cerevisiae E3 ubiquitin ligase/putative helicase Irc20 as a regulator of HR. Using purified Irc20, we show that it can hydrolyze ATP in the presence and absence of DNA, but does not increase access to DNA within a nucleosome. In addition, we show that both the ATPase and ubiquitin ligase activities of Irc20 are required for suppressing the spontaneous formation of recombination foci. Finally, we demonstrate a role for Irc20 in promoting Rad51 chromatin association and the removal of Rad52 recombinase from chromatin, thus facilitating subsequent HR steps and directing recombination to more error-free modes.

• PMID: 33202365
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Reference Type

Journal Article | Research Support, Non-U.S. Gov't

Authors

Jalal D, Chalissery J, Iqbal M, Hassan AH

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