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And-1 coordinates with CtIP for efficient homologous recombination and DNA damage checkpoint maintenance.


ABSTRACT: 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 the mechanism 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.

SUBMITTER: Chen Y 

PROVIDER: S-EPMC5389581 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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And-1 coordinates with CtIP for efficient homologous recombination and DNA damage checkpoint maintenance.

Chen Yali Y   Liu Hailong H   Zhang Haoxing H   Sun Changqing C   Hu Zhaohua Z   Tian Qingsong Q   Peng Changmin C   Jiang Pei P   Hua Hui H   Li Xinzhi X   Pei Huadong H  

Nucleic acids research 20170301 5


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 the mechanism is still not fully understood. Here, we establish that And-1, a replisome component, promotes DNA-end resection and DNA repair by homologous recombination. Mech  ...[more]

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