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Elucidation of transcription-coupled chromosomal translocation pathways between gene loci

Research Project

Project/Area Number 20K21536
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 50:Oncology and related fields
Research InstitutionGunma University

Principal Investigator

Shibata Atsushi  群馬大学, 未来先端研究機構, 准教授 (30707633)

Co-Investigator(Kenkyū-buntansha) 山内 基弘  九州大学, アイソトープ統合安全管理センター(馬出地区), 准教授 (60437910)
安原 崇哲  東京大学, 大学院医学系研究科(医学部), 助教 (90757056)
Project Period (FY) 2020-07-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2021: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
KeywordsDNA二本鎖切断 / 放射線 / 染色体転座 / DNA切断 / 発がん / 転写共役型DNA修復
Outline of Research at the Start

本研究では最新の分子生物学的手法を導入し、これまで困難とされたヒト静止期細胞における染色体転座の分子メカニズムの解明を目標にする。本研究の達成により、ヒト成体の大半を占める静止期細胞がどのようにしてDNA損傷から遺伝情報を守り、発がんを抑制しているのかが明らかになる。もう一つの波及効果として、医療分野の面では、G1期に停止しているがん幹細胞の化学療法剤・放射線治療時の細胞致死誘導メカニズムの解明に繋がると考えている。

Outline of Final Research Achievements

Chromosomal translocations that are critical to tumorigenesis are caused by misrepair of DNA double-strand break (DSB). However, the processes by which chromosomal translocations between gene loci that lead to tumorigenesis is largely unknown. In the research project, we aimed to examine DSB-induced chromosomal translocation between transcriptionally active loci by establishing a human cultured cell experimental system that artificially induces DSBs at arbitrary locations and timings. We constructed a system in which the restriction enzyme AsiSI is induced into the nucleus by tamoxifen analog, 40HT, in retinal pigment epithelial cells, and created an assay for detecting DSB chromosomal translocation.

Academic Significance and Societal Importance of the Research Achievements

DNA二本鎖切断(DSB: DNA double strand break)は、その修復エラーにより重篤なゲノム不安定化を引き起こす。実際、DSB修復異常によって引き起こされるゲノム不安化はがん発症に強く繋がることから、DSB修復研究は人の健康維持に必要不可欠な研究課題である。本研究課題では、発がんに繋がるゲノム不安定化の中でも特に重篤な染色体転座の発生機構の研究を行った。その原理解明は、人体における発がん抑制のための治療戦略の開発に繋がる。

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (49 results)

All 2023 2022 2021 2020 Other

All Int'l Joint Research (2 results) Journal Article (20 results) (of which Int'l Joint Research: 18 results,  Peer Reviewed: 20 results,  Open Access: 13 results) Presentation (24 results) (of which Int'l Joint Research: 4 results,  Invited: 19 results) Remarks (3 results)

  • [Int'l Joint Research] サセックス大学(英国)

    • Related Report
      2021 Research-status Report
  • [Int'l Joint Research] サセックス大学(英国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Analysis of the relationship between LET, γH2AX foci volume and cell killing effect of carbon ions using high-resolution imaging technology2023

    • Author(s)
      Oike Takahiro、Kakoti Sangeeta、Sakai Makoto、Matsumura Akihiko、Ohno Tatsuya、Shibata Atsushi
    • Journal Title

      Journal of Radiation Research

      Volume: 64 Issue: 2 Pages: 335-344

    • DOI

      10.1093/jrr/rrac098

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Calreticulin Upregulation in Cervical Cancer Tissues From Patients After 10 Gy Radiation Therapy2023

    • Author(s)
      Okada Kohei、Sato Hiro、Kumazawa Takuya、Mori Yasumasa、Permata Tiara Bunga Mayang、Uchihara Yuki、Noda Shin-ei、Suzuki Keiji、Ikota Hayato、Yokoo Hideaki、Gondhowiardjo Soehartati、Nakano Takashi、Ohno Tatsuya、Shibata Atsushi
    • Journal Title

      Advances in Radiation Oncology

      Volume: 8 Issue: 3 Pages: 101159-101159

    • DOI

      10.1016/j.adro.2022.101159

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Carbon ion radiation and clustered DNA double-strand breaks2022

    • Author(s)
      Shibata Atsushi
    • Journal Title

      Enzymes

      Volume: 51 Pages: 117-130

    • DOI

      10.1016/bs.enz.2022.08.008

    • ISBN
      9780323993975
    • Related Report
      2022 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Radiosensitization by the Selective Pan-FGFR Inhibitor LY28744552022

    • Author(s)
      Darwis Narisa Dewi Maulany、Horigome Eisuke、Li Shan、Adachi Akiko、Oike Takahiro、Shibata Atsushi、Hirota Yuka、Ohno Tatsuya
    • Journal Title

      Cells

      Volume: 11 Issue: 11 Pages: 1727-1727

    • DOI

      10.3390/cells11111727

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DNA damage promotes HLA class I presentation by stimulating a pioneer round of translation-associated antigen production2022

    • Author(s)
      Uchihara Yuki、Permata Tiara Bunga Mayang、Sato Hiro、Kawabata-Iwakawa Reika、Katada Sayako、Gu Wenchao、Kakoti Sangeeta、Yamauchi Motohiro、Kato Reona、Gondhowiardjo Soehartati、Hosen Naoki、Yasuhara Takaaki、Shibata Atsushi
    • Journal Title

      Molecular Cell

      Volume: 82 Issue: 14 Pages: 2557-2570.e7

    • DOI

      10.1016/j.molcel.2022.04.030

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] RAP80 suppresses the vulnerability of R-loops during DNA double-strand break repair2022

    • Author(s)
      Yasuhara Takaaki、Kato Reona、Yamauchi Motohiro、Uchihara Yuki、Zou Lee、Miyagawa Kiyoshi、Shibata Atsushi
    • Journal Title

      Cell Reports

      Volume: 38 Issue: 5 Pages: 110335-110335

    • DOI

      10.1016/j.celrep.2022.110335

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Expression of non-homologous end joining factor, Ku80, is negatively correlated with PD-L1 expression in cancer cells after X-ray irradiation2021

    • Author(s)
      Kumazawa Takuya、Mori Yasumasa、Sato Hiro、Permata Tiara、Uchihara Yuki、Noda Shin-Ei、Okada Kohei、Kakoti Sangeeta、Suzuki Keiji、Ikota Hayato、Yokoo Hideaki、Gondhowiardjo Soehartati、Nakano Takashi、Ohno Tatsuya、Shibata Atsushi
    • Journal Title

      Oncology Letters

      Volume: 23 Issue: 1 Pages: 29-29

    • DOI

      10.3892/ol.2021.13147

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 64Cu-ATSM Predicts Efficacy of Carbon Ion Radiotherapy Associated with Cellular Antioxidant Capacity2021

    • Author(s)
      Nachankar Ankita、Oike Takahiro、Hanaoka Hirofumi、Kanai Ayaka、Sato Hiro、Yoshida Yukari、Obinata Hideru、Sakai Makoto、Osu Naoto、Hirota Yuka、Takahashi Akihisa、Shibata Atsushi、Ohno Tatsuya
    • Journal Title

      Cancers

      Volume: 13 Issue: 24 Pages: 6159-6159

    • DOI

      10.3390/cancers13246159

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genome Maintenance Mechanisms at the Chromatin Level2021

    • Author(s)
      Takatsuka Hirotomo、Shibata Atsushi、Umeda Masaaki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10384-10384

    • DOI

      10.3390/ijms221910384

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] ATM’s Role in the Repair of DNA Double-Strand Breaks2021

    • Author(s)
      Shibata Atsushi、Jeggo Penny A.
    • Journal Title

      Genes

      Volume: 12 Issue: 9 Pages: 1370-1370

    • DOI

      10.3390/genes12091370

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Mechanism of chromosome rearrangement arising from single-strand breaks2021

    • Author(s)
      Kot Palina、Yasuhara Takaaki、Shibata Atsushi、Hirakawa Miyako、Abe Yu、Yamauchi Motohiro、Matsuda Naoki
    • Journal Title

      Biochemical and Biophysical Research Communications

      Volume: 572 Pages: 191-196

    • DOI

      10.1016/j.bbrc.2021.08.001

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] High linear energy transfer carbon-ion irradiation upregulates PD-L1 expression more significantly than X-rays in human osteosarcoma U2OS cells2021

    • Author(s)
      Permata Tiara Bunga Mayang、Sato Hiro、Gu Wenchao、Kakoti Sangeeta、Uchihara Yuki、Yoshimatsu Yukihiko、Sato Itaru、Kato Reona、Yamauchi Motohiro、Suzuki Keiji、Oike Takahiro、Tsushima Yoshito、Gondhowiardjo Soehartati、Ohno Tatsuya、Yasuhara Takaaki、Shibata Atsushi
    • Journal Title

      Journal of Radiation Research

      Volume: 62 Issue: 5 Pages: 773-781

    • DOI

      10.1093/jrr/rrab050

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Modulation of immune responses by DNA damage signaling2021

    • Author(s)
      Uchihara Yuki、Permata Tiara Bunga Mayang、Sato Hiro、Shibata Atsushi
    • Journal Title

      DNA Repair

      Volume: 104 Pages: 103135-103135

    • DOI

      10.1016/j.dnarep.2021.103135

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Analysis of radiotherapy induced alteration of CD8+ T cells and PD-L1 expression in patients with uterine cervical squamous cell carcinoma2021

    • Author(s)
      Mori Yasumasa、Sato Hiro、Kumazawa Takuya、Permata Tiara、Yoshimoto Yuya、Murata Kazutoshi、Noda Shin-Ei、Kaminuma Takuya、Ando Ken、Oike Takahiro、Okonogi Noriyuki、Okada Kohei、Kakoti Sangeeta、Suzuki Keiji、Ikota Hayato、Yokoo Hideaki、Nakano Takashi、Ohno Tatsuya、Shibata Atsushi
    • Journal Title

      Oncology Letters

      Volume: 21 Issue: 6 Pages: 446-446

    • DOI

      10.3892/ol.2021.12707

    • Related Report
      2021 Research-status Report 2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Quantitative volumetric analysis of the Golgi apparatus following X-ray irradiation by super-resolution 3D-SIM microscopy2021

    • Author(s)
      Oike Takahiro、Uchihara Yuki、Permata Tiara Bunga Mayang、Gondhowiardjo Soehartati、Ohno Tatsuya、Shibata Atsushi
    • Journal Title

      Medical Molecular Morphology

      Volume: - Issue: 2 Pages: 166-172

    • DOI

      10.1007/s00795-020-00277-z

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] UBC13-Mediated Ubiquitin Signaling Promotes Removal of Blocking Adducts from DNA Double-Strand Breaks2020

    • Author(s)
      Akagawa Remi、Trinh Hai Thanh、Saha Liton Kumar、Tsuda Masataka、Hirota Kouji、Yamada Shintaro、Shibata Atsushi、Kanemaki Masato T.、Nakada Shinichiro、Takeda Shunichi、Sasanuma Hiroyuki
    • Journal Title

      iScience

      Volume: 23 Issue: 4 Pages: 101027-101027

    • DOI

      10.1016/j.isci.2020.101027

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] RNF8 promotes high linear energy transfer carbon-ion-induced DNA double-stranded break repair in serum-starved human cells2020

    • Author(s)
      Nakajima Nakako Izumi、Yamauchi Motohiro、Kakoti Sangeeta、Cuihua Liu、Kato Reona、Permata Tiara Bunga Mayang、Iijima Moito、Yajima Hirohiko、Yasuhara Takaaki、Yamada Shigeru、Hasegawa Sumitaka、Shibata Atsushi
    • Journal Title

      DNA Repair

      Volume: 91-92 Pages: 102872-102872

    • DOI

      10.1016/j.dnarep.2020.102872

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles for 53BP1 in the repair of radiation-induced DNA double strand breaks2020

    • Author(s)
      Shibata Atsushi、Jeggo Penny A.
    • Journal Title

      DNA Repair

      Volume: 93 Pages: 102915-102915

    • DOI

      10.1016/j.dnarep.2020.102915

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] DNA Repair and Signaling in Immune-Related Cancer Therapy2020

    • Author(s)
      Kakoti Sangeeta、Sato Hiro、Laskar Siddhartha、Yasuhara Takaaki、Shibata Atsushi
    • Journal Title

      Frontiers in Molecular Biosciences

      Volume: 7 Pages: 205-205

    • DOI

      10.3389/fmolb.2020.00205

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Roles for the DNA-PK complex and 53BP1 in protecting ends from resection during DNA double-strand break repair2020

    • Author(s)
      Shibata Atsushi、Jeggo Penny A
    • Journal Title

      Journal of Radiation Research

      Volume: 61 Issue: 5 Pages: 718-726

    • DOI

      10.1093/jrr/rraa053

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Regulation of immune-ligand presentation in response to DNA damage.2023

    • Author(s)
      柴田 淳史
    • Organizer
      The 19th Ataxia-Telangiectasia workshop
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 放射線治療と免疫チェックポイント阻害剤併用時の最適化を目指した基礎医学研究2023

    • Author(s)
      柴田 淳史
    • Organizer
      第23回菅原・大西記念癌治療増感研究シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 放射線照射後に生じるDNA損傷を起因とする腫瘍免疫応答の研究2022

    • Author(s)
      柴田 淳史
    • Organizer
      QST病院講演
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 教育講演 生物「放射線の細胞への影響」2022

    • Author(s)
      柴田 淳史
    • Organizer
      日本放射線腫瘍学会第35回学術大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] DNA二本鎖切断修復の経路選択性に影響するクロマチン構造変化の解析2022

    • Author(s)
      柴田 淳史
    • Organizer
      第95回日本生化学会大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] The mechanism underlying HLA Class I presentation in response to DNA damage2022

    • Author(s)
      柴田 淳史
    • Organizer
      The 29th Federation of Asian and Oceanian Biochemists and Molecular Biologists Conference & the 2022 Chinese Society of Biochemistry and Molecular Biology Online Conference
    • Related Report
      2022 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA損傷に応答する免疫リガンド発現制御機構2022

    • Author(s)
      柴田 淳史
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 分子生物学に基づく放射線照射後の細胞応答の可視化2022

    • Author(s)
      柴田 淳史
    • Organizer
      日本放射線影響学会第65回大会
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] DNA損傷応答により活性化される免疫リガンド発現制御機構2022

    • Author(s)
      柴田 淳史
    • Organizer
      第3回若手人材育成セミナー
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] 放射線治療時に生じる DNA 損傷を起因とする腫瘍免疫応答の研究2022

    • Author(s)
      柴田 淳史
    • Organizer
      第27回癌治療増感研究会 シンポジウム
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Presentation] DNA損傷により促進されるHLA Class I提示機構2022

    • Author(s)
      柴田 淳史
    • Organizer
      第9回DNA損傷応答ワークショップ Online
    • Related Report
      2022 Annual Research Report
  • [Presentation] Immune responses regulated by DNA damage signaling2022

    • Author(s)
      柴田 淳史
    • Organizer
      12th International Symposium Gunma University Initiative for Advanced Research (GIAR)、Hybrid conference
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 放射線の細胞への影響2022

    • Author(s)
      柴田 淳史
    • Organizer
      日本放射線腫瘍学会 第12回放射線生物学セミナー
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] Radiation-induced DNA damage and repair: a look into carbon-ion dependent Clustered DNA Double Strand Breaks2021

    • Author(s)
      柴田 淳史
    • Organizer
      International Training Course on Carbon Ion Radiotherapy 2021
    • Related Report
      2021 Research-status Report
    • Int'l Joint Research
  • [Presentation] 放射線照射が誘発する免疫応答の分子機構からみた放射線免疫治療併用の可能性.2021

    • Author(s)
      柴田 淳史
    • Organizer
      第62回日本肺癌学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 修復:線量によって変化するDNA修復機構.2021

    • Author(s)
      柴田 淳史
    • Organizer
      日本放射線腫瘍学会第34回学術大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 正確なDNA修復へと導くDNA二本鎖切断修復経路の決定メカニズム.2021

    • Author(s)
      柴田 淳史
    • Organizer
      第94回日本生化学会大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 放射線治療時に生じるDNA損傷を起因とする腫瘍免疫活性化の分子メカニズム.2021

    • Author(s)
      柴田 淳史
    • Organizer
      第59回日本癌治療学会学術集会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 放射線分子生物学の知見をどのようにして私たちの健康に役立てるのか?2021

    • Author(s)
      柴田 淳史
    • Organizer
      日本放射線影響学会 第64回大会
    • Related Report
      2021 Research-status Report
    • Invited
  • [Presentation] 放射線照射により惹起される免疫応答系リガンドの発現制御機構.2021

    • Author(s)
      柴田 淳史
    • Organizer
      第49回放射線による制癌シンポジウム
    • Related Report
      2021 Research-status Report
  • [Presentation] ゲノムの安定性維持機構の破綻による細胞影響から病態理解へ2020

    • Author(s)
      柴田 淳史
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 生命科学研究の最前線~生命の神秘を解き明かし、世界の医療発展に貢献する~2020

    • Author(s)
      柴田 淳史
    • Organizer
      群馬大学グローバルフロンティアリーダー(GFL)先端研究学際講演会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] G1期細胞におけるDNA二本鎖切断修復選択機構2020

    • Author(s)
      柴田 淳史
    • Organizer
      日本放射線影響学会第63回大会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Presentation] 転写活性領域におけるDNA二本鎖切断修復の経路選択機構2020

    • Author(s)
      柴田 淳史
    • Organizer
      第20回日本抗加齢医学会総会
    • Related Report
      2020 Research-status Report
    • Invited
  • [Remarks] 柴田研究室

    • URL

      https://shibataxlab.com/

    • Related Report
      2022 Annual Research Report
  • [Remarks] SHIBATA LAB

    • URL

      https://shibataxlab.com/english/

    • Related Report
      2022 Annual Research Report
  • [Remarks] 柴田研究室HP

    • URL

      https://shibataxlab.com/

    • Related Report
      2021 Research-status Report 2020 Research-status Report

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Published: 2020-08-03   Modified: 2024-01-30  

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