Phosphorylation of histone H2AX at M phase in human cells without DNA damage response
Phosphorylation of histone H2AX at M phase in human cells without DNA damage response
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DOI：
10.1016/j.bbrc.2005.08.164
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发表时间：
2005-10-28
影响因子：
3.1
通讯作者：
Teraoka, H
中科院分区：
文献类型：
--
作者：
Ichijima, Y;Sakasai, R;Teraoka, H
历史H2 A的变体H2 AX在响应DNA双链断裂（DSB）时在Ser 139上磷酸化，并且DSB诱导的细胞核中的磷酸化形式的H2 AX（γ-H2 AX）的簇在断裂位点处显示出病灶。在这里，我们显示磷酸化的H2 AX在细胞周期依赖性的方式没有任何可检测的DNA损伤反应。Western blot和免疫细胞化学分析表明，H2 AX在HeLa细胞中的M期被磷酸化。在缺乏ATM激酶活性的共济失调毛细血管扩张细胞中，在有丝分裂染色体中几乎检测不到γ-H2 AX，这表明ATM参与了H2 AX的M期磷酸化。单细胞凝胶电泳分析和蛋白质印迹分析与抗磷酸化p53（Ser 15）抗体表明，H2 AX在人类M期细胞磷酸化的DSB和DNA损伤信号的独立性。即使在没有DNA损伤的情况下，正常细胞周期进程中H2 AX的磷酸化也可能有助于维持基因组的完整性。(c)2005年爱思唯尔公司All rights reserved.
A variant of historic H2A, H2AX, is phosphorylated on Ser139 in response to DNA double-strand breaks (DSBs), and clusters of the phosphorylated form of H2AX (gamma-H2AX) in nuclei of DSB-induced cells show foci at breakage sites. Here, we show phosphorylation of H2AX in a cell cycle-dependent manner without any detectable DNA damage response. Western blot and immunocytochemical analyses with the anti-gamma-H2AX antibody revealed that H2AX is phosphorylated at M phase in HeLa cells. In ataxia-telangiectasia cells lacking ATM kinase activity, gamma-H2AX was scarcely detectable in the mitotic chromosomes, suggesting involvement of ATM in M-phase phosphorylation of H2AX. Single-cell gel electrophoresis assay and Western blot analysis with the anti-phospho-p53 (Ser15) antibody indicated that H2AX in human M-phase cells is phosphorylated independently of DSB and DNA damage signaling. Even in the absence of DNA damage, phosphorylation of H2AX in normal cell cycle progression may contribute to maintenance of genomic integrity. (c) 2005 Elsevier Inc. All rights reserved.