ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
2011 (English)In: EMBO Reports, ISSN 1469-221X, E-ISSN 1469-3178, Vol. 12, no 7, 713-719 p.Article in journal (Refereed) Published
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.
ATM, DNA damage response, double strand break repair, polynucleotide kinase/phosphatase, protein phosphorylation
IdentifiersURN: urn:nbn:se:su:diva-67006DOI: 10.1038/embor.2011.96ISI: 000292325700023OAI: oai:DiVA.org:su-67006DiVA: diva2:470019
authorCount :122011-12-282011-12-222011-12-28Bibliographically approved