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Molecular mechanism of genomic instability by RNA editing

Research Project

Project/Area Number 16K07251
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Molecular biology
Research InstitutionKyoto University

Principal Investigator

Kobayashi Maki  京都大学, 医学研究科, 特定准教授 (20400690)

Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2017: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2016: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords抗体遺伝子 / AID / クラススイッチ / 体細胞突然変異 / トポイソメラーゼ1 / 抗体遺伝子多様化 / クラススイッチ組換え / AICDA / miRNA / aicda / ゲノム不安定化 / RNA編集 / DNA切断
Outline of Final Research Achievements

One of the basic principles of "immunity" is the diversification of antibody genes, which is one of the mechanism of infection defense symbolized by the fact that you never suffer from measles twice. We elucidated a part of the complex story, how antibody genes are efficiently recombined in vivo to create a defense system. The topoisomerase 1 (Top1) presents in all the cells and have both function of maintenance of the integrity of the genomic DNA and also of destabilization the genomic DNA. By our study it was discovered that AID expressed only in immune B cells regulates Top1 by suppressing its translation and achieves highly efficient and specific gene recombination of antibody genes to produce diversified antibody proteins.

Academic Significance and Societal Importance of the Research Achievements

本研究を活かして抗体遺伝子組換えの効率化促進が可能になれば、感染防御システムを強化し、病原微生物の変化に迅速に対応する治療法が開発される可能性がある。トポイソメラーゼ1はすべての細胞に発現しているため、AID以外の細胞への刺激などがトポイソメラーゼ1の制御を介して細胞のがん化をもたらす分子機構が発見される可能性がある。また、トポイソメラーゼ1が不安定化することを防ぐ薬剤を発見できれば、一生の間にゲノムDNAに蓄積しがん化につながる遺伝子変異を最小限に抑えることができるかもしれない。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report
  • Research Products

    (11 results)

All 2019 2018 2017

All Journal Article (3 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (8 results) (of which Int'l Joint Research: 4 results,  Invited: 1 results)

  • [Journal Article] Apurinic/apyrimidinic endonuclease 1 (APE1) is dispensable for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation in the immunoglobulin gene.2019

    • Author(s)
      Helena Islam, Maki Kobayashi and Tasuku Honjo.
    • Journal Title

      International Immunology

      Volume: -- Issue: 8 Pages: 543-554

    • DOI

      10.1093/intimm/dxz028

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Depletion of recombination-specific cofactors by the C-terminal mutant of the activation-induced cytidine deaminase causes the dominant negative effect on class switch recombination.2017

    • Author(s)
      Al Ismail, A., Husain, A., Kobayashi, M., Honjo, T., Begum, N. A.
    • Journal Title

      International Immunology

      Volume: 29 Issue: 11 Pages: 525-537

    • DOI

      10.1093/intimm/dxx061

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] The novel activation-induced deoxycytidine deaminase (AID) mutants, AIDv and AIDvΔ15 are defective in SHM and CSR2017

    • Author(s)
      Maki Kobayashi, Misao Takemoto, Tasuku Honjo
    • Journal Title

      DNA Repair

      Volume: 印刷中 Pages: 1-3

    • DOI

      10.1016/j.dnarep.2017.02.015

    • Related Report
      2016 Research-status Report
  • [Presentation] Function of Sμ-germline transcripts in activation-induced cytidine deaminase (AID)-induced DNA breaks2018

    • Author(s)
      Maki Kobayashi, Misao Takemoto, Nasim A. Begum and Tasuku Honjo
    • Organizer
      The Keystone Symposia meeting on B Cells: Mechanisms in Immunity and Autoimmunity, 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] RNA-binding motifs of AID cofactor hnRNP K are necessary for inducing DNA breaks in IgH locus2018

    • Author(s)
      Ziwei Yin, Maki Kobayashi, Wenjun Hu, Nasim A. Begum, Tasuku Honjo
    • Organizer
      The Keystone Symposia meeting on B Cells: Mechanisms in Immunity and Autoimmunity, 2018
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Apurinic/apyrimidinic endonuclease 1 (APE1) is dispensable for activation-induced cytidine deaminase (AID)-dependent somatic hypermutation in the immunoglobulin gene2018

    • Author(s)
      Helena Islam, Maki Kobayashi and Tasuku Honjo
    • Organizer
      2nd International Symposium of Radiation Therapeutics and Biology
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] IgH遺伝子多様化におけるノンコーディング germline transcriptの機能2018

    • Author(s)
      小林 牧、本庶 佑
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] hnRNP KのRNA結合モチーフはAIDによる免疫グロブリン遺伝子多様化に必須である2018

    • Author(s)
      Ziwei Yin, Maki Kobayashi, Wenjun Hu, Nasim A. Begum, Tasuku Honjo
    • Organizer
      第41回日本分子生物学会年会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Topoisomerase 1 enrolls in diversification of Ig gene under the regulation of activation-induced cytidine deaminase (AID)2017

    • Author(s)
      Kobayashi, M and Honjo, T
    • Organizer
      International Symposium on Immune Diversity and Cancer Therapy Kobe 2017
    • Place of Presentation
      神戸市、ポートピアホテル
    • Year and Date
      2017-01-26
    • Related Report
      2016 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] Apurinic/Apyrimidinic endonuclease 1 (APE1)'s enrollment in activation induced cytidine deaminase (AID)-dependent IgH gene diversification2017

    • Author(s)
      Helena Islam、Maki Kobayashi、Tasuku Honjo
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report
  • [Presentation] クラススイッチ組換えにおけるメチルトランスフェラーゼFBLの役割2017

    • Author(s)
      森脇 隆仁、Afzal Husain、小林 牧、本庶 佑
    • Organizer
      生命科学系学会合同年次大会
    • Related Report
      2017 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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