• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Molecular mechanisms of action-at-a-distance mutations

Research Project

Project/Area Number 16H02956
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Risk sciences of radiation and chemicals
Research InstitutionHiroshima University

Principal Investigator

KAMIYA Hiroyuki  広島大学, 医系科学研究科(薬), 教授 (10204629)

Co-Investigator(Kenkyū-buntansha) 鈴木 哲矢  広島大学, 医歯薬保健学研究科(薬), 助教 (20573950)
小松 康雄  国立研究開発法人産業技術総合研究所, 生命工学領域, 研究グループ付 (30271670)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2016: ¥7,280,000 (Direct Cost: ¥5,600,000、Indirect Cost: ¥1,680,000)
KeywordsDNA損傷 / 遠隔作用変異 / DNA 損傷
Outline of Final Research Achievements

We established a system to detect action-at-a-distance mutations (untargeted mutations found at positions apart from a DNA lesion) by incorporating the DNA lesion of interest at a downstream position of the supF gene (a reporter gene for mutations). An oxidatively damaged base, 8-hydroxyguanine, was examined using this system and found to induce the action-at-a-distance mutations (base substitution mutations in this case) frequently when the WRN protein was reduced.
We also examined another kind of DNA lesion, an abasic site. We found that it induced the action-at-a-distance mutations observed in the 8-hydroxyguanine experiments and a different type of action-at-a-distance mutations (large deletions).

Academic Significance and Societal Importance of the Research Achievements

本研究の結果、WRN蛋白質(欠損すると癌易罹患性のある早老症であるWerner症候群が発症する)が減少すると、活性酸素により生ずるDNA損傷である8-hydroxyguanineにより遠隔作用変異が誘発されることが改めて示された。また、様々な原因で生じるabasic siteにより、別種の遠隔作用変異が誘発されることも示すことができ、DNAの損傷が従来考えられてきた以上に大きな影響をもたらすことが明らかとなった。

Report

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

    (21 results)

All 2018 2017 2016

All Journal Article (6 results) (of which Peer Reviewed: 6 results,  Open Access: 2 results,  Acknowledgement Compliant: 2 results) Presentation (15 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Reduction of Werner syndrome protein enhances G:C→A:T transition by O6-methylguanine in human cells.2018

    • Author(s)
      T. Suzuki, Y. Kuramoto and H. Kamiya
    • Journal Title

      Chem. Res. Toxicol.

      Volume: 31 Issue: 5 Pages: 319-324

    • DOI

      10.1021/acs.chemrestox.8b00009

    • Related Report
      2018 Annual Research Report 2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Mutations induced by 8-oxo-7,8-dihydroguanine in WRN- and DNA polymerase λ-double knockdown cells2018

    • Author(s)
      Kamiya Hiroyuki、Makino Tetsuaki、Suzuki Tetsuya、Kobayashi Miwako、Matsuoka Ichiro
    • Journal Title

      Mutagenesis

      Volume: 33 Issue: 4 Pages: 301-310

    • DOI

      10.1093/mutage/gey024

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Analysis of large deletion mutations induced by abasic site analog in human cells2018

    • Author(s)
      Suzuki Tetsuya、Katayama Yuri、Komatsu Yasuo、Kamiya Hiroyuki
    • Journal Title

      Genes and Environment

      Volume: 40 Issue: 1 Pages: 24-31

    • DOI

      10.1186/s41021-018-0110-7

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Comparison of DNA fragments as donor DNAs upon sequence conversion of cleaved target DNA2017

    • Author(s)
      Suzuki Tetsuya、Imada Takashi、Komatsu Yasuo、Kamiya Hiroyuki
    • Journal Title

      Nucleosides, Nucleotides and Nucleic Acids

      Volume: 36 Issue: 6 Pages: 428-434

    • DOI

      10.1080/15257770.2017.1310385

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Comparison of DNA fragments as donor DNAs upon sequence conversion of cleaved target DNA2017

    • Author(s)
      T. Suzuki, T. Imada, Y. Komatsu and H. Kamiya
    • Journal Title

      Nucleosides, Nucleotides, Nucleic Acids

      Volume: 36

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Mutations induced by 8-hydroxyguanine (8-oxo-7,8-dihydroguanine), a representative oxidized base, in mammalian cells2016

    • Author(s)
      T. Suzuki and H. Kamiya
    • Journal Title

      Genes Environment

      Volume: 39 Issue: 1

    • DOI

      10.1186/s41021-016-0051-y

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] DNA修復酵素APE1ノックダウンの脱塩基部位誘発欠失変異への影響2018

    • Author(s)
      紙谷浩之,片山友里,鈴木哲矢
    • Organizer
      第77回日本癌学会学術総会
    • Related Report
      2018 Annual Research Report
  • [Presentation] ヒト細胞における脱塩塩基部位アナログによるlarge deletionの誘発2018

    • Author(s)
      鈴木哲矢,片山友里,小松康雄,紙谷浩之
    • Organizer
      日本環境変異原学会第47回大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] Large deletion mutations induced by abasic site analog in human cells2018

    • Author(s)
      H. Kamiya, Y. Katayama, T. Suzuki, and Y. Komatsu
    • Organizer
      The 45th International Symposium on Nucleic Acids Chemistry
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Abasic siteによる欠失変異の誘発へのAPE1ノックダウンの影響2018

    • Author(s)
      片山友里,鈴木哲矢,小松康雄,紙谷浩之
    • Organizer
      第57回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2018 Annual Research Report
  • [Presentation] DNA損傷による変異誘発と相同組換えを利用するゲノム編集用核酸の開発.2018

    • Author(s)
      紙谷浩之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] 8-Hydroxyguanineによる遠隔作用変異を選択的に検出するアッセイ系の構築.2018

    • Author(s)
      井藤莉佳子,森まどか,鈴木哲矢,紙谷浩之
    • Organizer
      日本薬学会第138年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 標的DNAに切断を導入する配列変換におけるdonor核酸の比較.2017

    • Author(s)
      鈴木哲矢,今田貴士,小松康雄,紙谷浩之
    • Organizer
      日本ゲノム編集学会第2回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ヒト細胞において脱塩基部位が誘発する欠失変異.2017

    • Author(s)
      紙谷浩之,片山友里,鈴木哲矢
    • Organizer
      第76回日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 遠隔作用変異の抑制に関わる遺伝子のノックアウト細胞作製.2017

    • Author(s)
      森まどか,鈴木哲矢,紙谷浩之
    • Organizer
      第56回日本薬学会・日本薬剤師会・日本病院薬剤師会 中国四国支部学術大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] DNA損傷による変異とその防御.2017

    • Author(s)
      紙谷浩之
    • Organizer
      日本環境変異原学会第46回大会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] WRN によるO6-メチルグアニンが誘発する変異の抑制.2017

    • Author(s)
      鈴木哲矢,倉本佳枝,紙谷浩之
    • Organizer
      日本環境変異原学会第46回大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Large deletion mutations induced by an abasic site analogue in human cells.2017

    • Author(s)
      H. Kamiya, Y. Katayama, T. Suzuki, and Y. Komatsu
    • Organizer
      12th International Conference and 5th Asian Congress on Environmental Mutagens
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] WRNは、O6-メチルグアニンが誘発する変異を抑制する.2017

    • Author(s)
      倉本佳枝,鈴木哲矢,紙谷浩之
    • Organizer
      2017年度生命科学系学会合同年次大会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 酸化的損傷塩基8-ヒドロキシグアニンが誘発する遠隔作用変異2016

    • Author(s)
      紙谷浩之,牧野哲明,森まどか,鈴木哲矢
    • Organizer
      日本放射線影響学会第59回大会
    • Place of Presentation
      広島
    • Year and Date
      2016-10-27
    • Related Report
      2016 Annual Research Report
  • [Presentation] Werner syndrome proteinノックアウト細胞において8-ヒドロキシグアニンが誘発する変異2016

    • Author(s)
      紙谷浩之,森まどか,鈴木哲矢
    • Organizer
      第75回日本癌学会学術総会
    • Place of Presentation
      横浜
    • Year and Date
      2016-10-08
    • Related Report
      2016 Annual Research Report

URL: 

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

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi