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A Pathway of Double-Strand Break Rejoining Dependent upon ATM, Artemis, and Proteins Locating to ¿-H2AX Foci
journal contribution
posted on 2023-06-08, 00:54 authored by Enriqueta Riballo, Martin Kühne, Nicole Rief, Aidan DohertyAidan Doherty, Graeme C M Smith, Mari´a-José Recio, Caroline Reis, Kirsten Dahm, Andreas Fricke, Andrea Krempler, Antony R Parker, Stephen P Jackson, Andrew Gennery, Penny Jeggo, Markus LöbrichThe hereditary disorder ataxia telangiectasia (A-T) is associated with striking cellular radiosensitivity that cannot be attributed to the characterized cell cycle checkpoint defects. By epistasis analysis, we show that ataxia telangiectasia mutated protein (ATM) and Artemis, the protein defective in patients with RS-SCID, function in a common double-strand break (DSB) repair pathway that also requires H2AX, 53BP1, Nbs1, Mre11, and DNA-PK. We show that radiation-induced Artemis hyperphosphorylation is ATM dependent. The DSB repair process requires Artemis nuclease activity and rejoins approximately 10% of radiation-induced DSBs. Our findings are consistent with a model in which ATM is required for Artemis-dependent processing of double-stranded ends with damaged termini. We demonstrate that Artemis is a downstream component of the ATM signaling pathway required uniquely for the DSB repair function but dispensable for ATM-dependent cell cycle checkpoint arrest. The significant radiosensitivity of Artemis-deficient cells demonstrates the importance of this component of DSB repair to survival.
History
Publication status
- Published
Journal
Molecular CellISSN
1097-2765External DOI
Issue
5Volume
16Page range
715-724Pages
10.0Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
Notes
Designed project. Work done in PJ lab. Wrote paper. Desrcibes discovery of a pathway of double strand break repair defective in several disorders.Full text available
- No
Peer reviewed?
- Yes
Legacy Posted Date
2012-02-06Usage metrics
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