期刊
NUCLEIC ACIDS RESEARCH
卷 45, 期 5, 页码 2516-2530出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkw1212
关键词
-
资金
- National Basic Research Program of China 973 Program [2015CB910600, 2013CB910300]
- National Natural Science Foundation of China [31371433, 31571463, 81572740, 31301123]
- International S&T Cooperation Program of China [2015DFA31680, 2015DFA30610]
- State Key Laboratory of Proteomics [SKLP-O201303]
- One Thousand Young Talent Program
To prevent genomic instability, cells respond to DNA lesions by blocking cell cycle progression and initiating DNA repair. Homologous recombination repair of DNA breaks requires CtIP-dependent resection of the DNA ends, which is thought to play a key role in activation of CHK1 kinase to induce the cell cycle checkpoint. But themechanism is still not fully understood. Here, we establish that And-1, a replisome component, promotes DNA-end resection and DNA repair by homologous recombination. Mechanistically, And-1 interacts with CtIP and regulates CtIP recruitment to DNA damage sites. And-1 localizes to sites of DNA damage dependent on MDC1-RNF8 pathway, and is required for resistance to many DNA-damaging and replication stress-inducing agents. Furthermore, we show that And-1-CtIP axis is critically required for sustained ATR-CHK1 checkpoint signaling and for maintaining both the intra-S-and G2-phase checkpoints. Our findings thus identify And-1 as a novel DNA repair regulator and reveal how the replisome regulates the DNA damage induced checkpoint and genomic stability.
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