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γH2AX foci formation in the absence of DNA damage: Mitotic H2AX phosphorylation is mediated by the DNA‐PKcs/CHK2 pathway
Author(s) -
Tu Wen-Zhi,
Li Bing,
Huang Bo,
Wang Yu,
Liu Xiao-Dan,
Guan Hua,
Zhang Shi-Meng,
Tang Yan,
Rang Wei-Qing,
Zhou Ping-Kun
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.08.028
Subject(s) - dna damage , phosphorylation , mitosis , dna , microbiology and biotechnology , mitotic catastrophe , dna pkcs , checkpoint kinase 2 , biology , chemistry , biochemistry , protein serine threonine kinases , protein kinase a
Phosphorylated H2AX is considered to be a biomarker for DNA double‐strand breaks (DSB), but recent evidence suggests that γH2AX 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 γH2AX occurred in mitotic cells, and this increase was attenuated by DNA‐PKcs inactivation or Chk 2 depletion, but not by ATM inhibition. The phosphorylation‐mimic CHK2‐T68D abrogated the attenuation of mitotic γH2AX induced by DNA‐PKcs inactivation. Thus, the DNA‐PKcs/CHK2 pathway mediates the mitotic phosphorylation of H2AX in the absence of DNA damage.