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And-1 is required for homologous recombination repair by regulating DNA end resection.

ABSTRACT: Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA-binding protein 1 (And-1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is recruited to DNA DSB sites in a manner dependent on MDC1, BRCA1 and ATM, down-regulation of And-1 impairs end resection by reducing the recruitment of CtIP to damage sites, and considerably reduces Chk1 activation and other damage response during HR repair. These findings collectively demonstrate a hitherto unknown role of MDC1?And-1?CtIP axis that regulates CtIP-mediated DNA end resection and cellular response to DSBs.

SUBMITTER: Li Y

PROVIDER: S-EPMC5389477 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature

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And-1 is required for homologous recombination repair by regulating DNA end resection.

Li Yongming Y Li Zongzhu Z Wu Ruiqin R Han Zhiyong Z Zhu Wenge W

Nucleic acids research 20170301 5

Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA-binding protein 1 (And-1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is rec ...[more]

PMID: 27940557

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