ATM is the Predominant Kinase Involved in the Phosphorylation of Histone H2AX after Heating

• TAKAHASHI Akihisa

  Departments of Biology, School of Medicine, Nara Medical University

• MORI Eiichiro

  Departments of Biology, School of Medicine, Nara Medical University

• SU Xiaoming

  Departments of Biology, School of Medicine, Nara Medical University

• NAKAGAWA Yosuke

  Departments of Oral and Maxillofacial Surgery, School of Medicine, Nara Medical University

• OKAMOTO Noritomo

  Departments of Biology, School of Medicine, Nara Medical University Departments of Otorhinolaryngology, School of Medicine, Nara Medical University

• UEMURA Hirokazu

  Departments of Biology, School of Medicine, Nara Medical University Department of Head and Neck Surgery, Osaka Medical Center for Cancer

• KONDO Natsuko

  Departments of Biology, School of Medicine, Nara Medical University

• NODA Taichi

  Departments of Biology, School of Medicine, Nara Medical University

• TOKI Atsushi

  Departments of Biology, School of Medicine, Nara Medical University

• EJIMA Yosuke

  Division of Molecular Radiation Biology, Department of Radiation Oncology, University of Texas Southwestern Medical Center

• CHEN David J.

  Department of Radiological Sciences, Hiroshima Prefectural College of Health Sciences

• OHNISHI Ken

  Departments of Biology, School of Medicine, Nara Medical University

• OHNISHI Takeo

  Departments of Biology, School of Medicine, Nara Medical University

Abstract

Heating induces histone H2AX phosphorylation at serine 139 (γH2AX). Phosphorylated H2AX subsequently forms foci in numerous mammalian cell lines. The aim of this study was to clarify details in the mechanisms involved in the phosphorylation of H2AX after heating. The cell lines used were DNA-PKcs knockout cells, ATM knockout cells, and their parental cell lines. To elucidate mechanisms of induction of phosphorylation of H2AX after heating, ATM/ATR inhibitor (CGK733) and DNA-PK inhibitor (NU7026) were used. The intensity of γH2AX signals was assayed with flow cytometry. The thermal dose-response curve for the fluorescence intensity of γH2AX appearance in DNA-PKcs–/– cells during the heating period was similar to that observed in DNA-PKcs+/+ cells. On the other hand, the slope of thermal dose-response curve for them in ATM–/– cells was lower than that in ATM+/+ cells. Phosphorylation of H2AX after heating was suppressed by a combination of CGK733 and NU7026 in the culture medium in DNA-PKcs–/– cells, ATM–/– cells and in their parental cells. Although the phosphorylation of H2AX after heating was not suppressed by NU7026 in their parental cells, such phosphorylation was suppressed by CGK733 in their parental cells. These results indicate that ATM is the predominant protein which is active in the phosphorylation of histone H2AX after heating.

Journal

• Journal of Radiation Research

  Journal of Radiation Research 51 (4), 417-422, 2010

  Journal of Radiation Research Editorial Committee

Keywords

• Hyperthermia
• γH2AX
• ATM
• DNA-PK

Details

• CRID: 1390001205215546496
• NII Article ID: 10026563899
• NII Book ID: AA00705792
• DOI: 10.1269/jrr.10015
• ISSN: 13499157
• ISSN: 04493060
• NDL BIB ID: 10766066
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I10766066
• Web Site: http://academic.oup.com/jrr/article-pdf/51/4/417/3294087/jrr-51-417.pdf
• Web Site: https://search.jamas.or.jp/link/ui/2011079609
• Text Lang: en
• Data Source:
  • JaLC
  • NDL
  • Crossref
  • CiNii Articles
  • KAKEN
• Abstract License Flag: Disallowed