Histone H2AX participates the DNA damage-induced ATM activation through interaction with NBS1

Journal Article · Fri Mar 20 04:00:00 EDT 2009 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/j.bbrc.2009.01.109· OSTI ID:21255937

Kobayashi, Junya ^[1]; Tauchi, Hiroshi ^[2]; Chen, Benjamin; Bruma, Sandeep ^[3]; Tashiro, Satoshi ^[4]; Matsuura, Shinya ^[5]; Tanimoto, Keiji ^[6]; Chen, David J ^[3]; Komatsu, Kenshi ^[1]

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1. Department of Genome Repair Dynamics, Radiation Biology Center, Kyoto University, Kyoto 606-8501 (Japan)
2. Department of Environmental Sciences, Ibaraki University, Ibaraki 310-8512 (Japan)
3. Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas, Southwestern Medical Center at Dallas, Dallas, TX 75390-9187 (United States)
4. Department of Cellular Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan)
5. Department of Radiation Biology, Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima 734-8553 (Japan)
6. 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, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 4 Vol. 380; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANTIBODIES
CELL CYCLE
CHROMATIN
DNA
HISTONES
IN VITRO
INTERACTIONS
IRRADIATION
PHOSPHORYLATION
STRAND BREAKS