Protein phosphatase 1γ is responsible for dephosphorylation of histone H3 at Thr 11 after DNA damage

The DNA-damage-induced transcriptional suppression of cell cycle regulatory genes correlates with a reduction in histone H3-Thr 11 phosphorylation (H3-pThr 11) on their promoters that is partly mediated by the dissociation of Chk1 from chromatin. In this study, we identify protein phosphatase 1 gamma (PP1 gamma) as a phosphatase responsible for DNA-damage-induced H3-pThr 11 dephosphorylation. PP1 gamma is activated after DNA damage, which is mainly mediated by a reduction in Cdk-dependent phosphorylation of PP1 gamma at Thr 311. The depletion of PP1 gamma sensitizes HCT116 cells to DNA damage. Our results suggest that the ataxia telangiectasia, mutated and Rad3-related-Chk1 axis regulates H3-pThr 11 dephosphorylation on DNA damage, at least in part by the activation of PP1 gamma through Chk1-dependent inhibition of Cdks.