Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation
Abstract
The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. However, the mechanism of ATM activation during genotoxicstress is only partially understood. Here we report a direct regulatory linkage between the protein serine-threonine phosphatase 5 (PP5) and ATM. PP5 interacts with ATM in a DNA-damage-inducible manner. Reduced expression of PP5 attenuated DNA-damage-induced activation of ATM. Expression of a catalytically inactive PP5 mutant inhibited the phosphorylation of ATM substrates and the autophosphorylation of ATM on Ser 1981, and caused an S-phase checkpoint defect in DNA-damaged cells. Together our findings indicate that PP5 plays an essential role in the activation and checkpoint signaling functions of ATM in cells that have suffered DNA double-strand breaks.
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Footnotes
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Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1176004.
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Supplemental material is available at http://www.genesdev.org.
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↵4 These authors contributed equally to this work.
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↵5 Corresponding author. E-MAIL wang0011{at}mc.duke.edu; FAX (919) 681-7152.
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- Accepted December 22, 2003.
- Received December 2, 2003.
- Cold Spring Harbor Laboratory Press
