Proof of mutual interference between two DNA double strand break sites leading to chromosomal translocation

• Project/Area Number: 15H02816
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Gunma University
• Principal Investigator: Niimi Atsuko 群馬大学, 未来先端研究機構, 助教 (50508984)
• Research Collaborator: SHIBATA Atsushi 群馬大学, 大学院医学系研究科, 研究講師 (30707633) ; YAMAUCHI Motohiro 長崎大学, 学内共同利用施設等, 助教 (60437910)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000); Fiscal Year 2017: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2015: ¥5,980,000 (Direct Cost: ¥4,600,000、Indirect Cost: ¥1,380,000)
• Keywords: 染色体転座 / DNA修復 / 53BP1 / DNA二本鎖切断 / 重粒子線

Outline of Final Research Achievements

We established LacO-I-SceI-TetO cell line and tried to set up a new system for monitoring chromosomal translocation, however unfortunately, it was not working well because of technical problems. It is well known that the particle irradiation more frequently causes chromosomal translocation compared with X-ray irradiation. Therefore we simultaneously visualized the site of IR-induced DSBs and chromosome position by combining Immunofluorescence and FISH after C-ion or X-rays irradiation. We found that the frequency of gH2AX foci at the chromosome boundary of chromosome 1 after C-ion irradiation was >4-fold higher than that after X-ray irradiation, and gH2AX foci at chromosome boundaries after C-ion irradiation contain DSBs undergoing DNA-end resection, which promotes repair utilizing microhomology mediated end-joining during translocation. These data suggest that the spatial proximity between breaks is an important factor in translocation formation.

Research Products

• [Int'l Joint Research] Silpakorn University(タイ)
• [Journal Article] 3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread γH2AX foci after high LET heavy-ion particle radiation (2017)
  • Author(s): Hagiwara Yoshihiko、Niimi Atsuko、Isono Mayu、Yamauchi Motohiro、Yasuhara Takaaki、Limsirichaikul Siripan、Oike Takahiro、Sato Hiro、Held Kathryn D.、Nakano Takashi、Shibata Atsushi
  • Journal Title: Oncotarget Volume: 8 Issue: 65 Pages: 109370-109381
  • DOI: 10.18632/oncotarget.22679
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] BRCA1 directs the repair pathway to homologous recombination by promoting 53BP1 dephosphorylation (2017)
  • Author(s): Mayu Isono, Atsuko Niimi, Takahiro Oike, Yoshihiko Hagiwara, Hiro Sato, Ryota Sekine, Yukari Yoshida, Shin-Ya Isobe, Chikashi Obuse, Ryotaro Nishi, Elena Petricci, Shinichiro Nakada, Takashi Nakano, Atsushi Shibata
  • Journal Title: Cell Reports Volume: 18 Issue: 2 Pages: 520-532
  • DOI: 10.1016/j.celrep.2016.12.042
  • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Regulation of pairing between broken DNA-containing chromatin regions by Ku80, DNA-PKcs, ATM, and 53BP1 (2017)
  • Author(s): Motohiro Yamauchi, Atsushi Shibata, Keiji Suzuki, Masatoshi Suzuki, Atsuko Niimi, Hisayoshi Kondo, Miwa Miura, Miyako Hirakawa, Keiko Tsujita, Shunichi Yamashita, Naoki Matsuda
  • Journal Title: Scientific Reports Volume: 7 Issue: 1 Pages: 41812-41812
  • DOI: 10.1038/srep41812
  • NAID: 120006987560
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Identification of DNA double strand breaks at chromosome boundaries along the track of particle irradiation (2016)
  • Author(s): Atsuko Niimi, Motohiro Yamauchi, Siripan Limsirichaikul, Ryota Sekine, Takahiro Oike, Hiro Sato, Keiji Suzuki, Kathryn D. Held, Takashi Nakano, Atsushi Shibata
  • Journal Title: Genes Chromosomes & Cancer Volume: 55 Issue: 8 Pages: 650-660
  • DOI: 10.1002/gcc.22367
  • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
• [Journal Article] Visualization of complex DNA double-strand breaks in a tumor treated with carbon ion radiotherapy (2016)
  • Author(s): Takahiro Oike, Atsuko Niimi, Noriyuki Okonogi, Kazutoshi Murata, Akihiko Matsumura, Shin-Ei Noda, Daijiro Kobayashi, Mototaro Iwanaga, Keisuke Tsuchida, Tatsuaki Kanai, Tatsuya Ohno, Atsushi Shibata, Takashi Nakano
  • Journal Title: Scientific Reports Volume: 6 Issue: 1 Pages: 22275-22275
  • DOI: 10.1038/srep22275
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] 超解像度顕微鏡による重粒子線誘発クラスターDNA二本鎖切断の空間的分布の解析 (2017)
  • Author(s): 新美敦子, 萩原慶彦, シリパンリムシリチャイクル, 尾池貴洋, 佐藤浩央, 中野隆史, 柴田淳史
  • Organizer: 第89回 日本遺伝学会
  • Invited
• [Presentation] 超解像度顕微鏡による重粒子線誘発クラスターDNA二本鎖切断の空間分布解析 (2017)
  • Author(s): 新美敦子, 萩原慶彦, シリパンリムシリチャイクル, 尾池貴洋, 佐藤浩央, 中野隆史, 柴田淳史
  • Organizer: 日本放射線影響学会 第60回大会
• [Presentation] 重粒子線に特徴的なDNA損傷の可視化と細胞運命決定に与える影響の解析 (2017)
  • Author(s): 新美敦子, 萩原慶彦, シリパンリムシリチャイクル, 尾池貴洋, 佐藤浩央, 中野隆史, 柴田淳史
  • Organizer: 2017年度生命科学系学会合同年次大会
• [Presentation] 重粒子線照射により誘発される特異なDNA損傷形状の可視化 (2016)
  • Author(s): 新美敦子, 山内基弘, シリパンリムシリチャイクル, 関根崚太, 磯野真由, 尾池貴洋, 佐藤浩央, 鈴木啓司, 中野隆史1, 柴田淳史
  • Organizer: 第39回 日本分子生物学会年会
  • Place of Presentation: パシフィコ横浜（横浜）
  • Year and Date: 2016-11-30
• [Presentation] Analysis of DNA synthesis during homologous recombination in G2 cells after ionizing irradiaiton (2016)
  • Author(s): Atsuko Niimi, Siripan Limsirichaikul, Takashi Nakano, Atsushi Shibata
  • Organizer: The 10th 3R symposium
  • Place of Presentation: Hotel Ichibata (Matsue)
  • Year and Date: 2016-11-13
  • Int'l Joint Research
• [Presentation] Analysis of cluster DNA double strand break formation using high-resolution microscopy (2016)
  • Author(s): Atsuko Niimi, Nakajima Izumi Nakako, Motohiro Yamauchi, Siripan Limsirichaikul, Takahiro Oike, Hiro Sato, Penny A. Jeggo, Kathryn D. Held, Takashi Nakano, Atsushi Shibata
  • Organizer: 10th Quinquennial Conference on Responses to DNA Damage
  • Place of Presentation: Egmond aan Zee (The Netherlands)
  • Year and Date: 2016-04-17
  • Int'l Joint Research
• [Presentation] 高LET重粒子線照射により誘発される２つの異なる染色体間にまたがるクラスターDNA損傷の同定 (2015)
  • Author(s): 新美敦子, 山内基弘, シリパンリムシリチャイクル, 関根崚太, 磯野真由, 尾池貴洋, 佐藤浩央, 鈴木啓司, 中野隆史, 柴田淳史
  • Organizer: 第38回日本分子生物学会年会 第88回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートアイランド(神戸）
  • Year and Date: 2015-12-01
• [Presentation] Visualization of heavy ion induced cluster DNA double strand breaks formation using the super-resolution microscopy (2015)
  • Author(s): Atsuko Niimi, Takahiro Oike, Mayu Isono, Yoshihiko Hagiwara, Yukari Yoshida, Akihisa Takahashi, Takashi Nakano, Atsushi Shibata
  • Organizer: 15th International Congress of Radiation Research
  • Place of Presentation: Kyoto International Conference Center(Kyoto)
  • Year and Date: 2015-05-25
  • Int'l Joint Research
• [Remarks] 重粒子線治療研究プログラム:新美助教 重粒子線治療の高い治療効果の一端を証明
  • URL: http://www.giar.gunma-u.ac.jp/topics/
• [Remarks] 重粒子線照射を受けた細胞に生じるDNA損傷の新たな特徴を発見
  • URL: http://www.med.gunma-u.ac.jp/newsrelease/3763.html
• [Remarks] 遺伝性乳がん卵巣がん症候群の原因遺伝子であるBRCA1の新たな機能を発見
  • URL: http://www.med.gunma-u.ac.jp/newsrelease/4230.html