Elucidation of the molecular mechanism of chromosome translocation formation/suppression after exposure to ionizing radiation

• Project/Area Number: 24710063
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Risk sciences of radiation/Chemicals
• Research Institution: Nagasaki University (2013-2014); Central Research Institute of Electric Power Industry (2012)
• Principal Investigator: YAMAUCHI Motohiro 長崎大学, 原爆後障害医療研究所, 助教 (60437910)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2014: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 染色体転座 / DNA二本鎖切断 / フォーカス / 会合 / Ku80 / DNA-PKcs / ATM / 53BP1 / 放射線 / 近接 / DNA-PK

Outline of Final Research Achievements

Chromosome translocation is a clinically relevant chromosome aberration since it can cause leukemia, solid cancer, or other diseases, yet the molecular mechanism for translocation formation/suppression is unknown. In the present study, we identified factors affecting interaction between multiple DNA double-strand breaks (DSBs), that is prerequisite for translocation formation. We visualized DSBs by “foci” of a DNA repair factor accumulating at DSB sites, and examined frequency of DSB interaction. We identify Ku80, DNA-PKcs, and ATM as factors suppressing DSB interaction, and we also find that 53BP1 promotes DSB interaction and thereby facilitates translocation formation.

Research Products

• [Journal Article] 放射線被ばく後にできる DNA 損傷に対するヒト細胞の防御機構 (2014)
  • Author(s): 山内基弘、三浦美和、松田尚樹
  • Journal Title: Japanese Journal of Radiation Safety Management Volume: 13 Issue: 1 Pages: 79-83
  • DOI: 10.11269/jjrsm.13.79
  • NAID: 130004941393
  • ISSN: 1347-1503, 1884-9512
  • Peer Reviewed / Open Access
• [Presentation] DNA二本鎖切断同士の会合に影響を与える因子 (2014)
  • Author(s): 山内基弘、鈴木啓司、柴田淳史、近藤久義、三浦美和、平川美弥子、山下俊一、松田尚樹
  • Organizer: 第37回日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-11-25
• [Presentation] DNA二本鎖切断同士の近接および染色体転座頻度に影響を与える因子 (2014)
  • Author(s): 山内基弘、鈴木啓司、柴田淳史、近藤久義、三浦美和、平川美弥子、山下俊一、松田尚樹
  • Organizer: 日本放射線影響学会第57回大会
  • Place of Presentation: かごしま県民交流センター、鹿児島県鹿児島市
  • Year and Date: 2014-10-03
• [Presentation] DNA二本鎖切断間の会合および染色体転座頻度に影響を与える因子 (2014)
  • Author(s): 山内基弘、柴田淳史、鈴木啓司
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜、神奈川県横浜市
  • Year and Date: 2014-09-27
• [Presentation] ATMによる染色体転座抑制機構 (2013)
  • Author(s): 山内基弘、鈴木啓司
  • Organizer: 第72回日本癌学会学術総会
  • Place of Presentation: 横浜市 パシフィコ横浜
• [Presentation] 染色体転座形成におけるp53 binding protein 1 (53BP1) の関与 (2013)
  • Author(s): 山内基弘、鈴木啓司、近藤久義、三浦美和、山下俊一、松田尚樹
  • Organizer: 第36回日本分子生物学会年会
  • Place of Presentation: 神戸市 神戸ポートアイランド
• [Presentation] Involvement of 53BP1 in a DNA double-strand break repair pathway that generates chromosome translocation. (2012)
  • Author(s): 山内基弘
  • Organizer: 日本放射線影響学会第55回大会
  • Place of Presentation: 東北大学川内北キャンパス（ 宮城県）