DNA end resection by CtIP and exonuclease 1 prevents genomic instability.
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.
Institute of Molecular Cancer Research, University of Zurich, Switzerland.
Wassim
W
Eid
Martin
M
Steger
Mahmoud
M
El-Shemerly
Lorenza P
LP
Ferretti
Javier
J
Peña-Diaz
Christiane
C
König
Emanuele
E
Valtorta
Alessandro A
AA
Sartori
Stefano
S
Ferrari
D002352:Carrier Proteins / Q000378:metabolism*; D045744:Cell Line, Tumor; D019610:Cytoprotection; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000378:metabolism*; D051747:DNA-Activated Protein Kinase / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases / Q000378:metabolism*; D042822:Genomic Instability; D057809:HEK293 Cells; D006801:Humans; D000076228:MRE11 Homologue Protein; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D011995:Recombination, Genetic / Q000235:genetics
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C121766:MRE11 protein, human; D009687:Nuclear Proteins; D051747:DNA-Activated Protein Kinase; C497263:PRKDC protein, human; C114331:EXO1 protein, human; D004706:Endodeoxyribonucleases; D005090:Exodeoxyribonucleases; D000076228:MRE11 Homologue Protein; C410741:RBBP8 protein, human; D045643:DNA Repair Enzymes