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Genomic instability by Topoisomerase 1 induced by AID-dependent RNA editing

Research Project

Project/Area Number 25440007
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(系)研究科(研究院), 准教授 (20400690)

Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2015: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2013: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Keywordsトポイソメラーゼ1 / AID / ゲノム不安定性 / 免疫グロブリン遺伝子 / 遺伝子不安定性 / Topoisomerase1 / miRNA / Ago2
Outline of Final Research Achievements

In order to identify the responsive site in Topoisomerase 1 (Top1) mRNA to AID, Top1 3'UTR knockout cells were generated from CH12 B lymphoma cells. Unexpectedly class switch recombination in these knockout cells was not abolished supposing that coding region of Top1 mRNA is the target of AID's regulation.
On the other hand, Top1's involvement in DNA cleavages in immunoglobulin (Ig) gene was further clarified by the proteasome inhibitor and the novel Top1 inhibitors. Additionally by Top1-GFP fusion protein and trapping by GFP, it is elucidated that FACT enrolls as an adopter molecule between Top1 and H3K4me3, modified histone with help of BRG1.

Report

(4 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • 2013 Research-status Report
  • Research Products

    (14 results)

All 2016 2015 2014 2013 Other

All Journal Article (8 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 8 results,  Open Access: 2 results,  Acknowledgement Compliant: 4 results) Presentation (5 results) (of which Int'l Joint Research: 1 results,  Invited: 1 results) Remarks (1 results)

  • [Journal Article] Chromatin remodeler SMARCA4 recruits topoisomerase 1 and suppresses transcription associated genomic instability2016

    • Author(s)
      Afzal Husain, Nasim A. Begum, Takako Taniguchi, Hisaaki Taniguchi, Maki Kobayashi, and Tasuku Honjo.
    • Journal Title

      Nat. Commu.

      Volume: 7 Issue: 1 Pages: 00-00

    • DOI

      10.1038/ncomms10549

    • NAID

      120006535056

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] LSD1/KDM1A promotes hematopoietic commitment of hemangioblasts through downregulation of Etv2.2015

    • Author(s)
      Takeuchi, M., Fuse, Y., Watanabe, M., Andrea, C.S., Takeuchi, M., Nakajima, H., Ohashi, K., Kaneko, H., Kobayashi-Osaki, M., Yamamoto, M. and Kobayashi, M.
    • Journal Title

      Proc. Natl. Acad. Sci. USA

      Volume: 112 Issue: 45 Pages: 13922-13927

    • DOI

      10.1073/pnas.1517326112

    • NAID

      120007135765

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] APE1 is dispensable for S region cleavage but required for its repair in class switch recombination2014

    • Author(s)
      Jianliang Xu, Afzal Husain, Wenjun Hu, Tasuku Honjo and Maki Kobayashi.
    • Journal Title

      PNAS USA

      Volume: 111 Issue: 48 Pages: 17242-17247

    • DOI

      10.1073/pnas.1420221111

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] C-terminal region of activation-induced cytidine deaminase (AID) is required for efficient class switch recombination and gene conversion.2014

    • Author(s)
      Sabouri S, Kobayashi M, Begum NA, Xu J, Hirota K, Honjo T
    • Journal Title

      Proc Natl Acad Sci U S A.

      Volume: 111 Issue: 6 Pages: 2253-2258

    • DOI

      10.1073/pnas.1324057111

    • NAID

      120005395696

    • Related Report
      2014 Research-status Report 2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models.2014

    • Author(s)
      Nguyen T, Xu J, Chikuma S, Hiai H, Kinoshita K, Moriya K, Koike K, Marcuzzi GP, Pfister H, Honjo T, Kobayashi M.
    • Journal Title

      Int Immunol

      Volume: 26 Issue: 7 Pages: 397-406

    • DOI

      10.1093/intimm/dxu040

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Activation-induced cytidine deaminase is dispensable for virus-mediated liver and skin tumor development in mouse models in press2014

    • Author(s)
      Tung Nguyen,Jianliang Xu,Shunsuke Chikuma,Hiroshi Hiai,Kazuo Kinoshita,Kyoji Moriya,Kazuhiko Koike,Gian Paolo Marcuzzi, Herbert Pfister, Tasuku Honjo, and Maki Kobayashi
    • Journal Title

      Int Immunol

      Volume: 未定

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] GATA factor switching from GATA2 to GATA1 contributes to erythroid differentiation2013

    • Author(s)
      Suzuki M, Kobayashi-Osaki M, Tsutsumi S, Pan X, Ohmori S, Takai J, Moriguchi T, Ohneda O, Ohneda K, Shimizu R, Kanki Y, Kodama T, Aburatani H, Yamamoto M
    • Journal Title

      Genes Cells

      Volume: 18 Issue: 11 Pages: 921-933

    • DOI

      10.1111/gtc.12086

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] In vivo analysis of Aicda gene regulation: a critical balance between upstream enhancers and intronic silencers governs appropriate expression2013

    • Author(s)
      Le Thi Huong, Maki Kobayashi,et al
    • Journal Title

      PLoSONE

      Volume: vol.8 Issue: 4 Pages: e61433-e61433

    • DOI

      10.1371/journal.pone.0061433

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Immunoglobulin gene diversification by activation-induced cytidine deaminase (AID) through Topoisomerase1 (Top1).2015

    • Author(s)
      Maki Kobayashi, Hiroyuki Wakaguri, Masakazu Shimizu, Koh-ichiro Higasa, Fumihiko Matsuda and Tasuku Honjo
    • Organizer
      The 2nd IFOM-Kyoto University Joint Symposium
    • Place of Presentation
      京都大学芝蘭会館
    • Year and Date
      2015-10-06
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research
  • [Presentation] トポイソメラーゼ1を介したAIDによる免疫グロブリン遺伝子の多様化2015

    • Author(s)
      小林 牧、本庶 佑
    • Organizer
      第17回RNA meeting
    • Place of Presentation
      札幌パークホテル
    • Year and Date
      2015-07-15
    • Related Report
      2015 Annual Research Report
  • [Presentation] Immunoglobulin gene diversification by activation-induced cytidine deaminase (AID) through Topoisomerase1 (Top1) .2015

    • Author(s)
      Maki Kobayashi, Jianliang Xu, Tasuku Honjo
    • Organizer
      The Golden Anniversary of B Cells Discovery, Keystone Symposia
    • Place of Presentation
      Fairmont Banff Springs, Banff, Canada
    • Year and Date
      2015-03-22 – 2015-03-26
    • Related Report
      2014 Research-status Report
  • [Presentation] AID-regulated Topoisomerase1 is the DNA cleaving enzyme during immunoglobulin diversification2014

    • Author(s)
      Maki Kobayashi
    • Organizer
      Kyoto University & National Taiwan University Symposium
    • Place of Presentation
      京都大学
    • Year and Date
      2014-09-01
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] AID regulates Top1 translation by changing miRNA loading to Top1 mRNA2014

    • Author(s)
      Maki Kobayashi, Masayuki Shimizu, Koichiro Higasa, Fumihiko Matsuda and Tasuku Honjo
    • Organizer
      Frontiers in Immunology 2014
    • Place of Presentation
      Novel Forum,Karolinska Institutet, Stockholm, Sweden
    • Year and Date
      2014-06-18 – 2014-06-21
    • Related Report
      2014 Research-status Report
  • [Remarks] 「AID-C末端によるDNAシナプス形成」について

    • URL

      http://www.kyoto-u.ac.jp/ja/news_data/h/h1/news6/2013_1/140128_2.htm

    • Related Report
      2013 Research-status Report

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Published: 2014-07-25   Modified: 2019-07-29  

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