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ATM-mediated phosphorylation of polynucleotide kinase/phosphatase is required for effective DNA double-strand break repair
- Segal-Raz, Hava (author)
- Mass, Gilad (author)
- Baranes-Bachar, Keren (author)
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- Lerenthal, Yaniv (author)
- Wang, Shih-Ya (author)
- Chung, Young Min (author)
- Ziv-Lehrman, Shelly (author)
- Hu, Mickey C. -T. (author)
- Chen, David J. (author)
- Shiloh, Yosef (author)
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- (creator_code:org_t)
- 2011-06-03
- 2011
- English.
- In: EMBO Reports. - : EMBO. - 1469-221X .- 1469-3178. ; 12:7, s. 713-719
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
Keyword
- ATM
- DNA damage response
- double strand break repair
- polynucleotide kinase/phosphatase
- protein phosphorylation
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Ziv-Lehrman, She ...
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- EMBO Reports
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- Stockholm University
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