DNA-PK:the Major Target for Wortmannin-mediated Radiosensitization by the Inhibition of DSB Repair via NHEJ Pathway

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概要

• 論文の詳細を見る

• The effect of wortmannin posttreatment was studied in cells derived from different species (hamster, mouse, chicken, and human) with normal and defective DNA-dependent protein kinase (DNA-PK) activity, cells with and without the ataxia telangiectasia (ATM) gene, and cells lacking other regulatory proteins involved in the DNA double-strand break (DSB) repair pathways. Clonogenic assays were used to obtain all results. Wortmannin radiosensitization was observed in Chinese hamster cells (V79-B310H , CHO-K1), mouse mammary carcinoma cells (SR-1), transformed human fibroblast (N2KYSV), chicken B lymphocyte wild-type cells (DT40), and chicken Rad54 knockout cells (Rad54^<-/->). However, mouse mammary carcinoma cells (SX9) with defects in the DNA-PK and chicken DNA-PK catalytic subunit (DNA-PKcs) knockout cells (DNA-PKcs^<-/-/->) failed to exhibit wortmannin radiosensitization. On the other hand, SCID mouse cells (SC3VA2) exposed to wortmannin exhibited significant increases in radiosensitivity, possibly because of some residual function of DNA-PKcs. Moreover, the transformed human cells derived from AT patients (AT2KYSV) and chicken ATM knockout cells (ATM^<-/->) showed pronounced wortmannin radiosensitization. These studies demonstrate confirm that the mechanism underlying wortmannin radiosensitization is the inhibition of DNA-PK, but not of ATM, thereby resulting in the inhibition of DSB repair via nonhomologous endjoining (NHEJ).

• 日本放射線影響学会の論文

著者

• UTSUMI HIROSHI

  Research Reactor Institute, Kyoto University

• Utsumi Hiroshi

  Research Reactor Institute Kyoto University

• Utsumi Hiroshi

  Health Res. Foundation

• Hashimoto Mitsumasa

  Kyoto Univ.

• Utsumi Hiroshi

  Kyoto Univ.

• TOKUNO Osamu

  Res. React. Inst. Kyoto Univ.

• Takata Minoru

  Dep. Of Late Effects Studies Radiation Biology Center Kyoto Univ.

• Takeda Shunichi

  Department Of Radiation Genetics Graduate School Of Medicine Kyoto University

• Takeda Shunichi

  Department Of Radiation Genetics Faculty Of Medicine Yoshidakonoe-cho Sakyo-ku Kyoto University

• Takeda Shunichi

  Dept. Radiat. Gen. Kyoto Univ.

• Hashimoto Mitsumasa

  Research Reactor Of Institute Kyoto Univ.

• Hashimoto Mitsumasa

  Research Reactor Institute Kyoto University

• Takata Minoru

  Immunology And Molecular Genetics Kawasaki Medical School

• Takata Minoru

  Dept. Of Cardiovascular Mol. Biol. Lederle Lab.

• Yamamoto Kazuo

  東北大学 生命科研究

• RAO SATISH

  Research Reactor Institute, Kyoto University

• TOKUNO OSAMU

  Research Reactor Institute, Kyoto University

• YAMAMOTO KEN-ICHI

  Department of Molecular Pathology, Cancer Research Institute, Kanazawa University

• Takeda Shunichi

  Department Of Radiation Genetics Faculty Of Medicine Kyoto University

• Yamamoto Ken-ichi

  Department Of Applied Physics Nagoya University:central Research Laboratory Hitachi Ltd.

• Yamamoto Kazuo

  大阪府立大学 生命環境科学部先端病態解析学

• Yamamoto K

  Department Of Molecular Pathology Cancer Research Institute Kanazawa University

• YAMAMOTO Kazuo

  Kanagawa Institute of Technology

• Utsumi H

  Research Reactor Institute Kyoto University

• Utsumi Hiroshi

  Research Reactor Institute

• Rao Satish

  Research Reactor Institute Kyoto University:department Of Radiobiology Kasturba Medical College

• Tokuno Osamu

  Research Reactor Institute Kyoto University

• Yamamoto K

  Kanagawa Institute Of Technology

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