Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
EMBO Rep. 2010 Nov;11(11):883-9. doi: 10.1038/embor.2010.152. Epub 2010 Oct 15.
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 1γ (PP1γ) as a phosphatase responsible for DNA-damage-induced H3-pThr 11 dephosphorylation. PP1γ is activated after DNA damage, which is mainly mediated by a reduction in Cdk-dependent phosphorylation of PP1γ at Thr 311. The depletion of PP1γ 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 PP1γ through Chk1-dependent inhibition of Cdks.
DNA 损伤诱导的细胞周期调控基因转录抑制与启动子上组蛋白 H3-Thr11 磷酸化（H3-pThr11）的减少相关，这种减少部分是由 Chk1 从染色质上解离介导的。在这项研究中，我们确定蛋白磷酸酶 1γ（PP1γ）是负责 DNA 损伤诱导的 H3-pThr11 去磷酸化的磷酸酶。PP1γ 在 DNA 损伤后被激活，主要是通过减少 Cdk 依赖性的 PP1γ 在 Thr311 上的磷酸化介导的。PP1γ 的耗竭使 HCT116 细胞对 DNA 损伤敏感。我们的结果表明，共济失调毛细血管扩张症突变和 Rad3 相关激酶 Chk1 通过 Chk1 依赖性抑制 Cdk 来调节 DNA 损伤时的 H3-pThr11 去磷酸化，至少部分是通过激活 PP1γ 实现的。
