γH2AX foci formation in the absence of DNA damage: Mitotic H2AX phosphorylation is mediated by the DNA-PKcs/CHK2 pathway

被引：114

作者：

Tu, Wen-Zhi ^{[1
,2
]}

Li, Bing ^{[2
]}

Huang, Bo ^{[1
]}

Wang, Yu ^{[2
]}

Liu, Xiao-Dan ^{[2
]}

Guan, Hua ^{[2
]}

Zhang, Shi-Meng ^{[2
]}

Tang, Yan ^{[1
]}

Rang, Wei-Qing ^{[1
]}

Zhou, Ping-Kun ^{[1
,2
]}

机构：

[1] Univ South China, Coll Publ Hlth, Inst Environm Med & Radiat Hyg, Hengyang 421000, Hunan, Peoples R China

[2] Beijing Inst Radiat Med, Dept Radiat Toxicol & Oncol, Beijing 100850, Peoples R China

来源：

FEBS LETTERS | 2013年 / 587卷 / 21期

基金：

国家高技术研究发展计划(863计划);

关键词：

gamma H2AX; CHK2; DNA-PKcs; DNA damage; Mitosis; DOUBLE-STRAND BREAKS; HISTONE H2AX; GENOMIC INSTABILITY; REPAIR; ATM; CELLS; CHECKPOINT; COMPLEX; KINASE; CHK2;

D O I：

10.1016/j.febslet.2013.08.028

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Phosphorylated H2AX is considered to be a biomarker for DNA double-strand breaks (DSB), but recent evidence suggests that gamma H2AX does not always indicate the presence of DSB. Here we demonstrate the bimodal dynamic of H2AX phosphorylation induced by ionizing radiation, with the second peak appearing when G2/M arrest is induced. An increased level of gamma H2AX occurred in mitotic cells, and this increase was attenuated by DNA-PKcs inactivation or Chk2 depletion, but not by ATM inhibition. The phosphorylation-mimic CHK2-T68D abrogated the attenuation of mitotic gamma H2AX induced by DNA-PKcs inactivation. Thus, the DNA-PKcs/CHK2 pathway mediates the mitotic phosphorylation of H2AX in the absence of DNA damage. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B. V. All rights reserved.

引用

页码：3437 / 3443

页数：7

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