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- Title
ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair.
- Authors
Segal-Raz, Hava; Mass, Gilad; Baranes-Bachar, Keren; Lerenthal, Yaniv; Wang, Shih-Ya; Chung, Young Min; Ziv-Lehrman, Shelly; Ström, Cecilia E; Helleday, Thomas; Hu, Mickey C-T; Chen, David J; Shiloh, Yosef
- Abstract
The cellular response to double-strand breaks (DSBs) in DNA is a complex signalling network, mobilized by the nuclear protein kinase ataxia-telangiectasia mutated (ATM), which phosphorylates many factors in the various branches of this network. A main question is how ATM regulates DSB repair. Here, we identify the DNA repair enzyme polynucleotide kinase/phosphatase (PNKP) as an ATM target. PNKP phosphorylates 5'-OH and dephosphorylates 3'-phosphate DNA ends that are formed at DSB termini caused by DNA-damaging agents, thereby regenerating legitimate ends for further processing. We establish that the ATM phosphorylation targets on human PNKP-Ser 114 and Ser 126-are crucial for cellular survival following DSB induction and for effective DSB repair, being essential for damage-induced enhancement of the activity of PNKP and its proper accumulation at the sites of DNA damage. These findings show a direct functional link between ATM and the DSB-repair machinery.
- Publication
EMBO reports, 2011, Vol 12, Issue 7, p713
- ISSN
1469-3178
- Publication type
Journal Article
- DOI
10.1038/embor.2011.96