And-1 is required for homologous recombination repair by regulating DNA end resection.
Nucleic Acids Res
; 45(5): 2531-2545, 2017 03 17.
Article
in En
| MEDLINE
| ID: mdl-27940557
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 MDC1âAnd-1âCtIP axis that regulates CtIP-mediated DNA end resection and cellular response to DSBs.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
DNA-Binding Proteins
/
DNA Breaks, Double-Stranded
/
Recombinational DNA Repair
Limits:
Humans
Language:
En
Journal:
Nucleic Acids Res
Year:
2017
Document type:
Article
Affiliation country:
United States