Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1
- Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan)
- Department of Environmental Sciences, Ibaraki University, Ibaraki 310-8512 (Japan)
- Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75390-9187 (United States)
- Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan)
- Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan)
- Department of Oral and Maxillofacial Radiology, Graduate School of Biomedical Sciences, Hiroshima University, Kasumi 1-2-3, Minami-ku, Hiroshima 734-8553 (Japan)
Phosphorylated histone H2AX ({gamma}-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 {gamma}-H2AX at DSB sites following its auto-phosphorylation. However, it is unclear whether {gamma}-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 {gamma}-H2AX-dependent manner. Foci formation of phosphorylated ATM and ATM-dependent phosphorylation is repressed in H2AX-knockdown cells. Furthermore, anti-{gamma}-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, {gamma}-H2AX has important role for effective DSB-dependent activation of ATM-related damage responses via NBS1.
- OSTI ID:
- 21255937
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 380, Issue 4; Other Information: DOI: 10.1016/j.bbrc.2009.01.109; PII: S0006-291X(09)00156-9; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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