title: γH2AX foci formation in the absence of DNA damage: mitotic H2AX phosphorylation is mediated by the DNA-PKcs/CHK2 pathway.
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 Chk2 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.
authors.affiliation: Institute for Environmental Medicine and Radiation Hygiene, The College of Public Health, University of South China, Hengyang, Hunan Province 421000, PR China; Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, PR China.
authors.forename: Wen-Zhi
authors.initials: WZ
authors.lastname: Tu
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Bo
authors.initials: B
authors.lastname: Huang
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiao-Dan
authors.initials: XD
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Guan
authors.forename: Shi-Meng
authors.initials: SM
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Tang
authors.forename: Wei-Qing
authors.initials: WQ
authors.lastname: Rang
authors.forename: Ping-Kun
authors.initials: PK
authors.lastname: Zhou
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D004247:DNA / Q000378:metabolism* / Q000528:radiation effects; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000528:radiation effects*; D009842:Oligopeptides / Q000378:metabolism*; D010766:Phosphorylation; D011839:Radiation, Ionizing; D015398:Signal Transduction
chemical_list: C468783:H2AX protein, human; D006657:Histones; D009842:Oligopeptides; C079676:lysyl-arginyl-alanyl-lysyl-alanyl-lysyl-threonyl-threonyl-lysyl-lysyl-arginine; D004247:DNA; D064447:Checkpoint Kinase 2; D064007:Ataxia Telangiectasia Mutated Proteins; C578634:CHEK2 protein, human
keywords: CHK2; DNA damage; DNA-PKcs; Mitosis; γH2AX