期刊
CELL REPORTS
卷 34, 期 13, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.celrep.2021.108906
关键词
-
类别
资金
- Fondazione AIRC [IG 2017-ID, 19783]
- Progetti di Ricerca di Interesse Nazionale (PRIN)
- Swiss National Science Foundation [31003A_175444]
- European Research Council [681630]
- European Research Council (ERC) [681630] Funding Source: European Research Council (ERC)
The MRX complex regulates its DNA binding and processing activities through transitions between different states, with Sae2 stimulating Mre11 endonuclease activity while Rif2 inhibits it. This dynamic regulation affects the retention of MRX at DSBs and checkpoint activation.
The Mre11-Rad50-Xrs2 (MRX) complex detects and processes DNA double-strand breaks (DSBs). Its DNA binding and processing activities are regulated by transitions between an ATP-bound state and a post-hydrolysis cutting state that is nucleolytically active. Mre11 endonuclease activity is stimulated by Sae2, whose lack increases MRX persistence at DSBs and checkpoint activation. Here we show that the Rif2 protein inhibits Mre11 endonuclease activity and is responsible for the increased MRX retention at DSBs in sae2 Delta cells. We identify a Rad50 residue that is important for Rad50-Rif2 interaction and Rif2 inhibition of Mre11 nuclease. This residue is located near a Rad50 surface that binds Sae2 and is important in stabilizing the Mre11-Rad50 (MR) interaction in the cutting state. We propose that Sae2 stimulates Mre11 endonuclease activity by stabilizing a post-hydrolysis MR conformation that is competent for DNA cleavage, whereas Rif2 antagonizes this Sae2 function and stabilizes an endonuclease inactive MR conformation.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据