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

作者：Li, Yongming; Li, Zongzhu; Wu, Ruiqin; Han, Zhiyong; Zhu, Wenge^*

来源：Nucleic Acids Research, 2017, 45(5): 2531-2545.

DOI：10.1093/nar/gkw1241

• DOUBLE-STRAND BREAKS
• SISTER-CHROMATID COHESION
• CELL-CYCLE
• POLYMERASE-ALPHA
• MRE11-RAD50-NBS1 COMPLEX
• SACCHAROMYCES-CEREVISIAE
• EUKARYOTIC REPLISOME
• GENOMIC STABILITY
• DAMAGE RESPONSE
• PROTEIN COMPLEX

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.

• 出版日期2017-3-17
• 单位大连医科大学