ΓH2AX foci formation in the absence of DNA damage: Mitotic H2AX phosphorylation is mediated by the DNA‐PKcs/CHK2 pathway. Issue 21 (8th September 2013)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: FEBS letters. Volume 587:Issue 21(2013)
• Page Start: 3437
• Page End: 3443
• Publication Date: 2013-09-08
• Subjects: γH2AX -- CHK2 -- DNA-PKcs -- DNA damage -- Mitosis; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1016/j.febslet.2013.08.028
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : A second peak of H2AX phosphorylation appears when G2/M arrest is induced by ionizing radiation. An increased level of γH2AX occurred in mitotic cells in the absence of DNA damage. The mitotic γH2AX can be attenuated by DNA‐PKcs inactivation, but not by ATM inhibition. DNA‐PKcs/CHK2 pathway mediates the mitotic phosphorylation of H2AX.