期刊
EMBO REPORTS
卷 11, 期 12, 页码 962-968出版社
WILEY
DOI: 10.1038/embor.2010.157
关键词
DNA double-strand break repair; CtIP; exonuclease 1; camptothecin
资金
- Swiss National Science Foundation (SNF)
- UBS Foundation
- Novartis Foundation for Medical and Biological Research
- Desiree and Niels Yde Foundation
- University of Zurich Research Priority Program (URPP)
- Vontobel-Foundation
- Swiss National Science Foundation (SNSF)
- University of Zurich
End resection of DNA-which is essential for the repair of DNA double-strand breaks (DSBs) by homologous recombination-relies first on the partnership between MRE11-RAD50-NBS1 (MRN) and CtIP, followed by a processive step involving helicases and exonucleases such as exonuclease 1 (EXO1). In this study, we show that the localization of EXO1 to DSBs depends on both CtIP and MRN. We also establish that CtIP interacts with EXO1 and restrains its exonucleolytic activity in vitro. Finally, we show that on exposure to camptothecin, depletion of EXO1 in CtIP-deficient cells increases the frequency of DNA-PK-dependent radial chromosome formation. Thus, our study identifies new functions of CtIP and EXO1 in DNA end resection and provides new information on the regulation of DSB repair pathways, which is a key factor in the maintenance of genome integrity.
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