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A DNA damage-independent role for 53BP1 in apoptotic cells

Research Project

Project/Area Number 26281025
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypePartial Multi-year Fund
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionKanazawa Medical University

Principal Investigator

IWABUCHI Kuniyoshi  金沢医科大学, 医学部, 教授 (10232696)

Co-Investigator(Kenkyū-buntansha) 逆井 良  金沢医科大学, 医学部, 助教 (10549950)
砂谷 優実  金沢医科大学, 医学部, 講師 (70581057)
石垣 靖人  金沢医科大学, 総合医学研究所, 教授 (20232275)
Co-Investigator(Renkei-kenkyūsha) NAKAMURA Akira  金沢医科大学, 医学部, 教授 (20344723)
Project Period (FY) 2014-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥16,380,000 (Direct Cost: ¥12,600,000、Indirect Cost: ¥3,780,000)
Fiscal Year 2016: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2015: ¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥9,490,000 (Direct Cost: ¥7,300,000、Indirect Cost: ¥2,190,000)
Keywords53BP1 / DNA二重鎖切断 / アポトーシス / 細胞生物学 / DNA損傷修復 / 分子生物学
Outline of Final Research Achievements

53BP1 accumulates at sites of DNA double-strand breaks (DSBs), and facilitates non-homologous end joining repair of DSBs. We found that 53BP1 is cleaved into a fragment in a caspase-dependent manner in apoptotic cells. This 53BP1 cleavage was observed in apoptosis induced by not only X-ray irradiation, but also treatment with staurosporine, a non-DNA damaging apoptosis-inducer. Some of the 53BP1 fragments are localized on the surface of apoptotic cells. The surface localization of the 53BP1 fragment was observed in apoptotic cells which lacked expression of RNF8 or RNF168, ubiquitin ligases required for accumulation of 53BP1 at DSB sites. These data suggest that in apoptotic cells, 53BP1 plays a role independent on the role of 53BP1 in DNA damage responses.

Report

(5 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Annual Research Report
  • 2015 Annual Research Report
  • 2014 Annual Research Report
  • Research Products

    (26 results)

All 2018 2017 2016 2015 2014

All Journal Article (7 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 7 results,  Open Access: 3 results,  Acknowledgement Compliant: 1 results) Presentation (19 results) (of which Int'l Joint Research: 3 results)

  • [Journal Article] Caspase-mediated cleavage of X-ray repair cross-complementing group 4 promotes apoptosis by enhancing nuclear translocation of caspase- activated DNase2018

    • Author(s)
      1.Sunatani Y, Kamdar RP, Sharma MK, Matsui T, Sakasai R, Hashimoto M, Ishigaki Y, Matsumoto Y, Iwabuchi K
    • Journal Title

      Exp Cell Res

      Volume: 362 Issue: 2 Pages: 450-460

    • DOI

      10.1016/j.yexcr.2017.12.009

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Aquarius is required for proper CtIP expression and homologous recombination repair2017

    • Author(s)
      2.Sakasai R, Isono M, Wakasugi M, Hashimoto M, Sunatani Y, Matsui T, Shibata A, Matsunaga T, Iwabuchi K
    • Journal Title

      Sci Rep

      Volume: 7 Issue: 1 Pages: 1-11

    • DOI

      10.1038/s41598-017-13695-4

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phosphorylation of EB2 by Aurora B and CDK1 ensures mitotic progression and genome stability.2016

    • Author(s)
      Iimori M, Watanabe S, Kiyonari S, Matsuoka K, Sakasai R, Saeki H, Oki E, Kitao H, Maehara Y:
    • Journal Title

      Nature Communications

      Volume: [Epub ahead of print] Issue: 1 Pages: 11117-11117

    • DOI

      10.1038/ncomms11117

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA double-strand breaks induced intractable glomerular fibrosis in renal allografts.2016

    • Author(s)
      Matsui Y, Sunatani Y, Hayashi N, Okino K, Okushi Y, Mukai K, Adachi H, Yamaya H, Iwabuchi K, Yokoyama H
    • Journal Title

      Clin. Exp. Nephrol.

      Volume: 20 Issue: 3 Pages: 479-488

    • DOI

      10.1007/s10157-015-1174-3

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Caspase-3/7-mediated cleavage of β2-spectrin is required for acetaminophen-induced liver damage.2016

    • Author(s)
      Baek HJ, Lee YM, Kim TH, Kim JY, Park EJ, Iwabuchi K, Mishra L, Kim SS.
    • Journal Title

      Int J Biol Sci.

      Volume: 12 Issue: 2 Pages: 172-183

    • DOI

      10.7150/ijbs.13420

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The distinctive cellular responses to DNA strand breaks caused by a DNA topoisomerase I poison in conjunction with DNA replication and RNA transcription2015

    • Author(s)
      Sakasai R, Iwabuchi K.
    • Journal Title

      Genes & Genetic Systems

      Volume: 90 Issue: 4 Pages: 187-194

    • DOI

      10.1266/ggs.15-00023

    • NAID

      130005118395

    • ISSN
      1341-7568, 1880-5779
    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Protein kinase CK2 is required for the recruitment of 53BP1 to sites of DNA double-strand break induced by radiomimetic drugs.2014

    • Author(s)
      Guerra B, Iwabuchi K, Issinger OG.
    • Journal Title

      Cancer Lett

      Volume: 345 Issue: 1 Pages: 115-123

    • DOI

      10.1016/j.canlet.2013.11.008

    • Related Report
      2014 Annual Research Report
    • Peer Reviewed
  • [Presentation] ユビキチン化因子UBE2E2によるDNAトポイソメラーゼIIの制御2017

    • Author(s)
      逆井良, 砂谷優実, 松井理, 岩淵邦芳
    • Organizer
      第24回DNA複製・組換え・修復ワークショップ
    • Related Report
      2017 Annual Research Report
  • [Presentation] NA二本鎖切断修復タンパク質53BP1を介した神経前駆細胞の未分化性維持機構2017

    • Author(s)
      砂谷優実, 逆井良, 松井理, 橋本光正, 岩淵邦芳
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Analysis of repair pathway for one-ended DNA double-strand breaks2017

    • Author(s)
      Sakasai R, Sunatani Y, Matsui T, Iwabuchi K
    • Organizer
      日本放射線影響学会第60回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] PARP- and TDP1-dependent repair pathways of one-ended DNA double-strand breaks caused by camptothecin2017

    • Author(s)
      逆井良, 砂谷優実, 松井理, 岩淵邦芳
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] RNAヘリカーゼAquariusはDNA-RNAハイブリッドを解消して相同組換え修復を促進する2016

    • Author(s)
      逆井 良, 磯野真由, 若杉光夫, 橋本光正, 砂谷優実, 松井 理, 柴田淳史, 松永 司, 岩淵邦芳
    • Organizer
      第39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
      2016-11-30
    • Related Report
      2016 Annual Research Report
  • [Presentation] DNA二本鎖切断修復タンパク質53BP1を介した神経前駆細胞の分化抑制効果2016

    • Author(s)
      砂谷優実, 辰野貴則, 中村有香, 逆井 良, 松井 理, 橋本光正, 石垣靖人, 岩淵邦芳
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ(広島県・広島市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] RNAヘリカーゼAquariusはR-loopを解消して相同組換え修復を促進する2016

    • Author(s)
      逆井 良, 磯野真由, 若杉光夫, 橋本光正, 砂谷優実, 松井 理, 柴田淳史, 松永 司, 岩淵邦芳
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      JMSアステールプラザ(広島県・広島市)
    • Year and Date
      2016-10-26
    • Related Report
      2016 Annual Research Report
  • [Presentation] Topoisomerase II switching is regulated by ubiquitination2016

    • Author(s)
      Sakasai R, Sunatani Y, Matsui T, Iwabuchi K
    • Organizer
      Gordon Research Conference, DNA Topoisomerase in Biology & Medicine
    • Place of Presentation
      Sunday River, Newry, ME, USA
    • Year and Date
      2016-08-07
    • Related Report
      2016 Annual Research Report
    • Int'l Joint Research
  • [Presentation] DNA修復タンパク質XRCC4のカスパーゼ依存性切断によるスプライシング調節を介したアポトーシスの促進2015

    • Author(s)
      砂谷優実, Kamdar RP, Sharma MK, 松井 理, 逆井 良, 橋本光正, 松本義久, 岩淵邦芳
    • 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
      神戸ポートピア(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Top2-poisonに対する主要調節因子であるユビキチン化酵素の同定2015

    • Author(s)
      逆井 良, 砂谷優実, 松井 理, 橋本光正, 岩淵邦芳
    • 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
      神戸ポートピア(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] p53標的遺伝子発現における53BP1の機能的役割2015

    • Author(s)
      松井 理, 逆井 良, 砂谷優実, 橋本光正, 岩淵邦芳
    • 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
      神戸ポートピア(兵庫県・神戸市)
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Phosphorylatio-mediated Regulation of Apoptosis By NHEJ-protein XRCC4Phosphorylatio-mediated Regulation of Apoptosis By NHEJ-protein XRCC42015

    • Author(s)
      Sunatani Y, Sharma MK, Kamdar RP, Matsui T, Sakasai R, Hashimoto M, Matsumoto Y, Iwabuchi K
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto International Conference Center (Kyoto)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ubiquitine-dependent Activation of DNA-PKcs Leads to Chromosomal Aberration in Response to One-ended DNA Double Strand Breaks2015

    • Author(s)
      Sakasai R, Sunatani Y, Matsui T, Hashimoto M, Iwabuchi K
    • Organizer
      15th International Congress of Radiation Research
    • Place of Presentation
      Kyoto International Conference Center (Kyoto)
    • Year and Date
      2015-05-25
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Ubiquitin-dependent activation of DNA-PKcs in response to DNA replication-mediated DNA double strand breaks.2014

    • Author(s)
      Sakasai R, Sunatani Y, Matsui T, Hashimoto M, Iwabuchi K.
    • Organizer
      The 9th 3R Symposium Together with National Institute of Genetics 2014 International Symposium.
    • Place of Presentation
      御殿場高原ホテル・時之栖(静岡県・御殿場市)
    • Year and Date
      2014-11-17 – 2014-11-21
    • Related Report
      2014 Annual Research Report
  • [Presentation] XRCC4のカスパーゼ依存的な切断によって引き起こされるアポトーシス促進の機構2014

    • Author(s)
      砂谷 優実, Radhika Pankaj Kamdar, Mukesh Kumar Sharma, 松井 理, 逆井 良, 橋本 光正, 松本 義久, 岩淵 邦芳.
    • Organizer
      第87回日本生化学会大会
    • Place of Presentation
      国立京都国際会館(京都府・京都市)
    • Year and Date
      2014-10-15 – 2014-10-18
    • Related Report
      2014 Annual Research Report
  • [Presentation] Role of RNA binding protein in cell cycle progression and centrosome maturation in human tumor cells.2014

    • Author(s)
      IshigakiY, Nakamura Y, Tatsuno T, Hashimoto M, Shimasaki T, Iwabuchi K, Tomosugi N.
    • Organizer
      19th World Congress on Advances in Oncology & 17th International Symposium of Molecular Medicine
    • Place of Presentation
      アテネ(ギリシャ)
    • Year and Date
      2014-10-09 – 2014-10-11
    • Related Report
      2014 Annual Research Report
  • [Presentation] ユビキチン化を介したDNA-PKcs 活性化機構2014

    • Author(s)
      逆井 良, 松井 理, 砂谷 優実, 橋本 光正, 岩淵 邦芳.
    • 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
      2014-10-01 – 2014-10-03
    • Related Report
      2014 Annual Research Report
  • [Presentation] 抗ガン剤トポイソメラーゼ阻害剤が引き起こす二次的DNA損傷に対する細胞応答2014

    • Author(s)
      逆井 良, 砂谷 優実, 松井 理, 橋本 光正, 岩淵 邦芳.
    • Organizer
      金沢医科大学医学会学術集会
    • Place of Presentation
      金沢医科大学(石川県・河北郡)
    • Year and Date
      2014-07-19
    • Related Report
      2014 Annual Research Report
  • [Presentation] Radiotoxicity after radioisotope therapy for bone metastases using & gamma-H2AX foci of DNA damage in lymphocytes.2014

    • Author(s)
      Doai M, Watanabe N, Takahashi T, Tonami H, Iwabuchi K.
    • Organizer
      第73回日本医学放射線学会総会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Year and Date
      2014-04-10 – 2014-04-13
    • Related Report
      2014 Annual Research Report

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Published: 2014-04-04   Modified: 2019-03-29  

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