Demonstration of persistent activation of ATM on translocated chromosomes by Foci on FISH method.

• Project/Area Number: 21710061
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Nagasaki University
• Principal Investigator: YAMAUCHI Motohiro 長崎大学, 大学院・医歯薬学総合研究科, 助教 (60437910)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 応答 / ATM / 染色体転座 / γ-H2AX / 細胞周期チェックポイント / DNA二重鎖切断 / H2AX / フォーカス / FISH

Research Abstract

I established" Foci on FISH" method, which combines immunofluorescence staining of phosphorylated histone H2AX and fluorescence in situ hybridization(FISH) of chromosomes. Using this technique, I demonstrated that H2AX phosphorylation, which indicates ATM activation, persists on dicentric chromosomes, a kind of chromosome translocation. Moreover, the present study revealed that ATM suppresses frequency of ionizing radiation-induced chromosome translocation via p53-dependent cell cycle checkpoint and DNA-PK-dependent DNA double-strand break repair pathway.

Research Products

• [Journal Article] Mode of ATM-dependent suppression of chromosome translocation (2011)
  • Author(s): 山内基弘、鈴木啓司、岡泰由、鈴木正敏、近藤久義、山下俊一
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 416巻 Pages: 111-118
  • NAID: 120006985345
  • Peer Reviewed
• [Journal Article] Persistence and dynamics of DNA damage signal amplification determined by microcolony formation and live-cell imaging (2011)
  • Author(s): 岡泰由、山内基弘、鈴木正敏、山下俊一、鈴木啓司
  • Journal Title: Journal of Radiation Research Volume: 52巻 Pages: 766-774
  • NAID: 10029653065
  • Peer Reviewed
• [Journal Article] Creating localized DNA double-strand breaks with microirradiation (2011)
  • Author(s): 鈴木啓司、山内基弘、岡泰由、鈴木正敏、山下俊一
  • Journal Title: Nature Protocols Volume: 6巻 Pages: 134-139
  • NAID: 120006985036
  • Peer Reviewed
• [Journal Article] ATM-dependent cellular response to DNA double strand breaks plays a pivotal role in the maintenance of the integrity of the genome (2011)
  • Author(s): 鈴木啓司、山内基弘、山下俊一
  • Journal Title: Radiation Protection Dosimetry Volume: 143巻 Pages: 279-283
  • NAID: 120006985149
  • Peer Reviewed
• [Journal Article] Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to ionizing radiation (2010)
  • Author(s): 石川彩、山内基弘、鈴木啓司、山下俊一
  • Journal Title: Genome Integrity Volume: 1巻 Pages: 10-10
  • NAID: 120006985122
  • Peer Reviewed
• [Journal Article] Requirement of ATM-dependent pathway for the repair of a subset of DNA double strand breaks created by restriction endonucleases (2010)
  • Author(s): 鈴木啓司、高橋麻衣子、岡泰由、山内基弘、鈴木正敏、山下俊一
  • Journal Title: Genome Integrity Volume: 1巻 Pages: 4-4
  • Peer Reviewed
• [Journal Article] A novel and simple micro-irradiation technique for creating localized DNA double-strand breaks (2010)
  • Author(s): 鈴木啓司、山内基弘、岡泰由、鈴木正敏、山下俊一
  • Journal Title: Nucleic Acids Research Volume: 38巻
  • NAID: 120006984199
  • Peer Reviewed
• [Journal Article] Image-based quantitative determination of DNA damage signal reveals a threshold for G2 checkpoint activation in response to ionizing radiation. (2010)
  • Author(s): 石川彩、山内基弘、鈴木啓司、山下俊一
  • Journal Title: Genome Integrity Volume: 1巻 Pages: 10-10
  • NAID: 120006985122
  • Peer Reviewed
• [Journal Article] Establishment of ponasterone A-inducible the wild-type p53 protein-expressing clones from HSC-1 cells, cell growth suppression by p53 expression and the suppression mechanism. (2009)
  • Author(s): Hori M, Suzuki K, Udono MU, Yamauchi M, Mine M, Watanabe M, Kondo S, Hozumi Y.
  • Journal Title: Archives of Dermatological Research 301 Pages: 631-646
  • Peer Reviewed
• [Journal Article] Microbeam irradiation facilities for radiobiology in Japan and China. (2009)
  • Author(s): Kobayashi Y, Funayama T, Hamada N, Sakashita T, Konishi T, Imaseki H, Yasuda K, Hatashita M, Takagi K, Yamashita S, Tomita M, Maeda M, Kobayashi K, Usami N, Wu L.
  • Journal Title: Journal of Radiation Research 50(Suppl.)
  • Peer Reviewed
• [Journal Article] Biological significance of DNA damage checkpoint and the mode of checkpoint signal amplification. (2009)
  • Author(s): Yamauchi M, Suzuki K, Yamashita S.
  • Journal Title: Acta Medica Nagasakiensia 53(Suppl.) Pages: 3-5
  • NAID: 110007050116
• [Presentation] 誤ったDNA二重鎖切断再結合部位に対するATM依存的チェックポイント応答 (2010)
  • Author(s): 山内基弘
  • Organizer: 日本放射線影響学会第53回大会
  • Place of Presentation: 京都
  • Year and Date: 2010-10-20
• [Presentation] 誤ったDNA二重鎖切断再結合部位に対するATM依存的チェックポイント応答 (2010)
  • Author(s): 山内基弘
  • Organizer: 日本放射線影響学会第53回大会、シンポジウム
  • Place of Presentation: 京都
• [Presentation] ATMによる染色体転座の認識 (2009)
  • Author(s): 山内基弘、鈴木啓司、山下俊一
  • Organizer: 日本放射線影響学会第52回大会
  • Place of Presentation: 広島
  • Year and Date: 2009-11-13
• [Presentation] ATMによる染色体転座の認識 (2009)
  • Author(s): 山内基弘、鈴木啓司、山下俊一
  • Organizer: 日本放射線影響学会第52回大会,ワークショップ
  • Place of Presentation: 広島
• [Presentation] ATM-p53 axis suppresses propagation of chromosome translocation by foci-growth-dependent G1 checkpoint (2009)
  • Author(s): 山内基弘
  • Organizer: Nagasaki Global COE program young investigators' international symposium,シンポジウム
  • Place of Presentation: 長崎