in DNA-damage-induced ATM activation

The checkpoint kinase ATM is centrally involved in the cellular response to DNA double-strand breaks. How-ever, the mechanism of ATM activation during geno-toxic 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. Re-duced expression of PP5 attenuated DNA-damage-in-duced 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 check-point signaling functions of ATM in cells that have suf-fered DNA double-strand breaks. Supplemental material is available a