DNA end resection by CtIP and exonuclease 1 prevents genomic instability.

Abstract	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.
Authors	Wassim Eid, Martin Steger, Mahmoud El-Shemerly, Lorenza P Ferretti, Javier Peña-Diaz, Christiane König, Emanuele Valtorta, Alessandro A Sartori, Stefano Ferrari
Journal	EMBO reports (EMBO Rep) Vol. 11 Issue 12 Pg. 962-8 (Dec 2010) ISSN: 1469-3178 [Electronic] England
PMID	21052091 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carrier Proteins DNA-Binding Proteins MRE11 protein, human Nuclear Proteins DNA-Activated Protein Kinase PRKDC protein, human EXO1 protein, human Endodeoxyribonucleases Exodeoxyribonucleases MRE11 Homologue Protein RBBP8 protein, human DNA Repair Enzymes
Topics	Carrier Proteins (metabolism) Cell Line, Tumor Cytoprotection DNA Breaks, Double-Stranded DNA Repair DNA Repair Enzymes (metabolism) DNA-Activated Protein Kinase (metabolism) DNA-Binding Proteins (metabolism) Endodeoxyribonucleases Exodeoxyribonucleases (metabolism) Genomic Instability HEK293 Cells Humans MRE11 Homologue Protein Nuclear Proteins (metabolism) Protein Binding Recombination, Genetic (genetics)

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