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ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
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2011 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 12, no 7, 713-719 p.Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
2011. Vol. 12, no 7, 713-719 p.
Keyword [en]
ATM, DNA damage response, double strand break repair, polynucleotide kinase/phosphatase, protein phosphorylation
National Category
Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-67006DOI: 10.1038/embor.2011.96ISI: 000292325700023OAI: oai:DiVA.org:su-67006DiVA: diva2:470019
Note
authorCount :12Available from: 2011-12-28 Created: 2011-12-22 Last updated: 2017-12-08Bibliographically approved

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Ström, Cecilia E.Helleday, Thomas
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Department of Genetics, Microbiology and Toxicology
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