Article
- The EMBO Journal (2009) 28, 3413 - 3427
- doi:10.1038/emboj.2009.276
Published online: 24 September 2009
Subject Categories:
ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2EMBO Open
Andrea Beucher1,3, Julie Birraux2,3, Leopoldine Tchouandong1,3, Olivia Barton1, Atsushi Shibata2, Sandro Conrad1, Aaron A Goodarzi2, Andrea Krempler1, Penny A Jeggo2 and Markus Löbrich1
- Darmstadt University of Technology, Radiation Biology and DNA Repair, Darmstadt, Germany
- Genome Damage and Stability Centre, University of Sussex, East Sussex, UK
Correspondence to:
Penny A Jeggo, Genome Damage and Stability Centre, University of Sussex, East Sussex BN1 9RQ, UK. Tel.: +44 1273 678482; Fax: +44 1273 678121; E-mail: p.a.jeggo@sussex.ac.uk
Markus Löbrich, Darmstadt University of Technology, Radiation Biology and DNA Repair, Darmstadt 64287, Germany. Tel.: +49 6151 167460; Fax: +49 6151 167462; E-mail: lobrich@bio.tu-darmstadt.de
3These authors contributed equally to this work
Received 22 June 2009; Accepted 6 August 2009
Abstract
Homologous recombination (HR) and non-homologous end joining (NHEJ) represent distinct pathways for repairing DNA double-strand breaks (DSBs). Previous work implicated Artemis and ATM in an NHEJ-dependent process, which repairs a defined subset of radiation-induced DSBs in G1-phase. Here, we show that in G2, as in G1, NHEJ represents the major DSB-repair pathway whereas HR is only essential for repair of 
15% of X- or 
-ray-induced DSBs. In addition to requiring the known HR proteins, Brca2, Rad51 and Rad54, repair of radiation-induced DSBs by HR in G2 also involves Artemis and ATM suggesting that they promote NHEJ during G1 but HR during G2. The dependency for ATM for repair is relieved by depleting KAP-1, providing evidence that HR in G2 repairs heterochromatin-associated DSBs. Although not core HR proteins, ATM and Artemis are required for efficient formation of single-stranded DNA and Rad51 foci at radiation-induced DSBs in G2 with Artemis function requiring its endonuclease activity. We suggest that Artemis endonuclease removes lesions or secondary structures, which inhibit end resection and preclude the completion of HR or NHEJ.
Keywords:
- Artemis,
- ataxia telangiectasia,
- double-strand breaks,
- homologous recombination,
- non-homologous end joining
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