title: 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.
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC 20037, USA.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC 20037, USA.
authors.forename: Zongzhu
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC 20037, USA.
authors.forename: Ruiqin
authors.initials: R
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC 20037, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Biochemistry and Molecular Medicine, The George Washington University School of Medicine and Health Science, 2300 Eye Street, N.W., Washington, DC 20037, USA.
authors.forename: Wenge
authors.initials: W
authors.lastname: Zhu
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004277:DNA, Single-Stranded / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D004706:Endodeoxyribonucleases; D006801:Humans; D009687:Nuclear Proteins / Q000378:metabolism; D059767:Recombinational DNA Repair
chemical_list: D002352:Carrier Proteins; D004277:DNA, Single-Stranded; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C544202:WDHD1 protein, human; C576597:ATR protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human