Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation.
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.
Ali, A; Zhang, J; Bao, S; Liu, I; Otterness, D; Dean, NM; Abraham, RT; Wang, X-F
Volume / Issue
Start / End Page
Pubmed Central ID
International Standard Serial Number (ISSN)
Digital Object Identifier (DOI)