蛋白磷酸酶 1γ负责 DNA 损伤后组蛋白 H3 上 Thr 11 的去磷酸化。
Protein phosphatase 1γ is responsible for dephosphorylation of histone H3 at Thr 11 after DNA damage.
机构信息
Department of Cell Biology, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.
出版信息
EMBO Rep. 2010 Nov;11(11):883-9. doi: 10.1038/embor.2010.152. Epub 2010 Oct 15.
Abstract
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.
摘要
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。
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