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Efficient suppression of random DNA integration

Research Project

Project/Area Number 18K19407
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 47:Pharmaceutical sciences and related fields
Research InstitutionYokohama City University

Principal Investigator

Adachi Noritaka  横浜市立大学, 生命ナノシステム科学研究科(八景キャンパス), 教授 (30264675)

Project Period (FY) 2018-06-29 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2018: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Keywords非相同末端連結 / ゲノム編集 / DNAポリメラーゼ / NHEJ
Outline of Final Research Achievements

In this research project, we have conducted a functional analysis of DNA polymerase theta, an essential protein for alternative end-joining-mediated DNA double-strand break repair. Additionally, using a cell-based screening method, we have screened compounds that inhibit human DNA polymerase theta. Our study will help develop a unique system to suppress DNA polymerase theta-mediated random integration, which will lead to human cell gene targeting with high efficiency.

Academic Significance and Societal Importance of the Research Achievements

本研究では、ヒト細胞に導入したベクターDNAが常に狙った位置に組み込まれるシステムの構築を目指し、その目標の一部を達成することができた。具体的には、DNAポリメラーゼθの重要な機能ドメインを明らかにしただけでなく、その活性を阻害する化合物の探索にも成功した。ランダム挿入の完全抑制の実現は高等動植物における安全で効率的なゲノム編集技術の確立に直結するため、本研究で得られた知見は今後幅広い分野に貢献するものと期待される。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • Research Products

    (5 results)

All 2019 2018 Other

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

  • [Int'l Joint Research] UNIST(韓国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] Complex genetic interactions between DNA polymerase β and the NHEJ ligase.2019

    • Author(s)
      Kurosawa A, Kuboshima H, Adachi N.
    • Journal Title

      FEBS J.

      Volume: 287 Issue: 2 Pages: 377-385

    • DOI

      10.1111/febs.15012

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Dynamic behavior of DNA topoisomerase IIβ in response to DNA double-strand breaks.2018

    • Author(s)
      Morotomi-Yano K, Saito S, Adachi N, Yano KI.
    • Journal Title

      Sci. Rep.

      Volume: 8 Issue: 1 Pages: 10344-10344

    • DOI

      10.1038/s41598-018-28690-6

    • NAID

      120006697280

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] ヒト細胞におけるDNAポリメラーゼθの機能解析2019

    • Author(s)
      吉川 真子
    • Organizer
      第42回日本分子生物学会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Role of Human DNA Polymerase θ at Double-Strand Breaks2018

    • Author(s)
      Saito S., Adachi N.
    • Organizer
      The 5th DNA polymerases meeting
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research / Invited

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Published: 2018-07-25   Modified: 2021-02-19  

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