Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection.

ABSTRACT: The Mre11-Rad50-Xrs2^NBS1 complex plays important roles in the DNA damage response by activating the Tel1^ATM kinase and catalyzing 5'-3' resection at DNA double-strand breaks (DSBs). To initiate resection, Mre11 endonuclease nicks the 5' strands at DSB ends in a reaction stimulated by Sae2^CtIP Accordingly, Mre11-nuclease deficient (mre11-nd) and sae2Δ mutants are expected to exhibit similar phenotypes; however, we found several notable differences. First, sae2Δ cells exhibit greater sensitivity to genotoxins than mre11-nd cells. Second, sae2Δ is synthetic lethal with sgs1Δ, whereas the mre11-nd sgs1Δ mutant is viable. Third, Sae2 attenuates the Tel1-Rad53^CHK2 checkpoint and antagonizes Rad9^53BP

SUBMITTER: Yu TY 

PROVIDER: S-EPMC6304958 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature