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Genes Dev. 2004 Feb 1;18(3):249-54.

Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation.

Author information

  • 1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA.

Abstract

The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. However, the mechanism of ATM activation during genotoxic stress 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.

PMID:
14871926
[PubMed - indexed for MEDLINE]
PMCID:
PMC338278
Free PMC Article

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