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ATM and Artemis promote homologous recombination of radiation-induced DNA double-strand breaks in G2

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posted on 2023-06-07, 15:11 authored by Andrea Beucher, Julie Birraux, Leopoldine Tchouandong, Olivia Barton, Atsushi Shibata, Sandro Conrad, Aaron A Goodarzi, Andrea Krempler, Penny Jeggo, Markus Lo¨brich
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

EMBO Journal

ISSN

0261-4189

Publisher

EMBO Press

Issue

21

Volume

28

Page range

3413-3427

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2009-11-20

First Open Access (FOA) Date

2018-03-16

First Compliant Deposit (FCD) Date

2018-03-16

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