The DNA damage tolerance (DDT) pathway facilitates the bypass of the fork-blocking lesions without removing them through either translesion DNA synthesis or error-free damage bypass mechanism. The Saccharomyces cerevisiae RAD5 is a multi-functional protein involved in the error-free branch of the DDT pathway, and its protein level periodically fluctuates through the cell cycle; however, the mechanistic basis and functional importance of the RAD5 level for the cell cycle regulation remain unclear. Here, we show that RAD5 is predominantly phosphorylated on serine 130 (S130) during S/G2 phase and that this modification depends on the cyclin-dependent kinase Cdc28/CDK1. We also show that the phosphorylated RAD5 species at S130 exhibit a relatively short half-life compared with non-phosphorylated RAD5 moiety, and that the RAD5 protein is partially stabilized in phosphorylation-defective RAD5 S130A cells. Importantly, the elimination of this modification results in a defective cell-cycle dependent RAD5 oscillation pattern. Together, our results demonstrate that CDK1 modulates RAD5 stability by phosphorylation during the cell cycle, suggesting a crosstalk between the phosphorylation and degradation of RAD5.

• PMID: 30256854
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Journal Article | Research Support, Non-U.S. Gov't

Authors

Hayashi M, Keyamura K, Hishida T

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