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DNA end resection by CtIP and exonuclease 1 prevents genomic instability
Author(s) -
Eid Wassim,
Steger Martin,
ElShemerly Mahmoud,
Ferretti Lorenza P,
PeñaDiaz Javier,
König Christiane,
Valtorta Emanuele,
Sartori Alessandro A,
Ferrari Stefano
Publication year - 2010
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.1038/embor.2010.157
Subject(s) - genome instability , exonuclease , rad50 , homologous recombination , helicase , dna repair , biology , dna damage , dna , olaparib , microbiology and biotechnology , non homologous end joining , genetics , dna binding protein , gene , poly adp ribose polymerase , polymerase , rna , transcription factor
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.