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DNA end resection by CtIP and exonuclease 1 prevents genomic instability

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

  • Wassim Eid
  • Martin Steger
  • Mahmoud El-Shemerly
  • Lorenza P Ferretti
  • Javier Pena Diaz
  • Christiane König
  • Emanuele Valtorta
  • Alessandro A Sartori
  • Stefano Ferrari

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.

OriginalsprogEngelsk
TidsskriftE M B O Reports
Vol/bind11
Udgave nummer12
Sider (fra-til)962-8
Antal sider7
ISSN1469-221X
DOI
StatusUdgivet - dec. 2010

ID: 138820827