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Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1 |
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| Authors: | Junya Kobayashi Hiroshi Tauchi Sandeep Bruma Shinya Matsuura David J. Chen |
| Affiliation: | a Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501, Japan b Department of Environmental Sciences, Ibaraki University, Ibaraki 310-8512, Japan c Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75390-9187, USA d Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan e Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553, Japan f Department of Oral and Maxillofacial Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553, Japan |
| Abstract: | Phosphorylated histone H2AX (γ-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 γ-H2AX at DSB sites following its auto-phosphorylation. However, it is unclear whether γ-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 γ-H2AX-dependent manner. Foci formation of phosphorylated ATM and ATM-dependent phosphorylation is repressed in H2AX-knockdown cells. Furthermore, anti-γ-H2AX antibody co-immunoprecipitates an ATM-like 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, γ-H2AX has important role for effective DSB-dependent activation of ATM-related damage responses via NBS1. |
| Keywords: | Histone H2AX ATM NBS1 DNA double-strand breaks Cell cycle checkpoint |
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