Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1
Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1
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DOI：
10.1016/j.bbrc.2009.01.109
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发表时间：
2009-03-20
影响因子：
3.1
通讯作者：
Komatsu, Kenshi
中科院分区：
文献类型：
--
作者：
Kobayashi, Junya;Tauchi, Hiroshi;Komatsu, Kenshi
磷酸化组蛋白H2AX （γ -H2AX）在DNA双链断裂（DSB）中招募DNA损伤反应蛋白并促进DSB修复中起作用。ATM也在其自磷酸化后与γ - h2ax在DSB位点共定位。然而，尚不清楚γ - h2ax是否在atm依赖性细胞周期检查点的激活中起作用。在这里，我们发现ATM和NBS1以依赖于γ - h2ax的方式被招募到受损的染色质上。在h2ax -敲低的细胞中，磷酸化ATM和ATM依赖性磷酸化的病灶形成受到抑制。此外，抗γ -H2AX抗体在体外共免疫沉淀了ATM样蛋白激酶活性，重组H2AX增加了未辐照细胞中ATM的体外激酶活性。此外，h2ax缺陷细胞在atm依赖的细胞周期检查点中表现出缺陷。综上所述，γ - h2ax在通过NBS1有效激活dsb依赖性的atm相关损伤反应中起着重要作用。(C) 2009爱思唯尔公司版权所有。
Phosphorylated histone H2AX (gamma-H2AX) functions in the recruitment of DNA damage response Proteins to DNA double-strand breaks (DSBs) and facilitates DSB repair. ATM also co-localizes with gamma-H2AX at DSB sites following its auto-phosphorylation. However, it is unclear whether gamma-H2AX has a role in activation of ATM-dependent cell cycle checkpoints. Here, we show that ATM as well as NBS1 is recruited to damaged-chromatin in a gamma-H2AX-dependent manner. Foci formation of phosphorylated ATM and ATM-dependent phosphorylation is repressed in H2AX-knockdown cells. Furthermore, anti-gamma-H2AX antibody co-immunoprecipitates an ATM-Iike protein kinase activity in vitro and recombinant H2AX increases in vitro kinase activity of ATM from un-irradiated cells. Moreover, H2AX-deficient cells exhibited a defect in ATM-dependent cell cycle checkpoints. Taken together, gamma-H2AX has important role for effective DSB-dependent activation of ATM-related damage responses via NBS1. (C) 2009 Elsevier Inc. All rights reserved.