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

Defects in a novel nucleotide excision repair factor leading to genomic instability in congenital dyskeratosis cells

Research Project

Project/Area Number 20K07308
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 48040:Medical biochemistry-related
Research InstitutionHamamatsu University School of Medicine

Principal Investigator

Niida Hiroyuki  浜松医科大学, 医学部, 准教授 (20336671)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsテロメラーゼ / 先天性角化症 / XPF / PRMT4 / telomere / NER / TRF2 / telomerase / テロメレース / シクロブタンピリミジンダイマー / ヌクレオチド除去修復
Outline of Research at the Start

我々はDCの原因遺伝子産物DKC1を含むテロメラーゼ複合体がNERを実行する上で必須の因子であると考えている。そこで解明を目指す点は次の事柄が挙げられる。
1) NERに関与するならば修復する損傷はテロメア領域に発生したものなのか。
2) テロメラーゼ複合体がNERのどのステップで関与するのか。
3) DCの発症・病態にNER欠損はどの様に関与するのか。
本研究を上記3つの課題に分け順次明らかにして行く。

Outline of Final Research Achievements

We found that the same telomerase complex factors are required for the removal of CPDs. We suspected an association with telomerase-mediated NER because XPF/ERCC1, a core factor of the nucleotide excision repair machinery (NER), is localised in the telomere region, but the regulation of XPF/ERCC1 activity is not known. We found that the arginine methyltransferase, PRMT4/CARM1, is required for the maintenance of XPF function. So far, it has been shown that methylation by PRMT4 affects the localisation of XPF-ERCC1 at sites of DNA damage and nuclease activity, which is largely due to changes in the binding capacity of XPF to ERCC1.

Academic Significance and Societal Importance of the Research Achievements

テロメア領域に生じたCPDが既知のNERによって修復されるのかわかっていない。我々はNERの進行にテロメラーゼのサブユニットTERT, TERC, DKCが必要とされることを明らかにした。これらテロメラーゼサブユニットの欠損は先天性角化症(DC)の原因となる。我々はテロメアに局在するNER因子ERCC1/XPFの機能制御にPRMT4が必要であることを見出した。XPFの活性はNERやICL repairに必須のヌクレアーゼであるとともにcisplatinなど抗癌剤に対する抵抗性に関わることが明らかにされており本研究の成果からDCに対する治療標的創出や薬剤耐性の軽減に寄与することが期待される。

Report

(4 results)
  • 2023 Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (9 results)

All 2022 2021 2020 Other

All Int'l Joint Research (1 results) Journal Article (6 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (2 results)

  • [Int'l Joint Research] Seoul National university(韓国)

    • Related Report
      2020 Research-status Report
  • [Journal Article] Chromatin-remodeling factor BAZ1A/ACF1 targets UV damage sites in an MLL1-dependent manner to facilitate nucleotide excision repair2022

    • Author(s)
      Koyauchi T, Niida H, Motegi A, Sakai S, Uchida C, Ohhata T, Iijima K, Yokoyama A, Suda T, Kitagawa M.
    • Journal Title

      Biochim Biophys Acta Mol Cell Res .

      Volume: 1869 Issue: 11 Pages: 119332-119332

    • DOI

      10.1016/j.bbamcr.2022.119332

    • Related Report
      2022 Research-status Report
    • Peer Reviewed
  • [Journal Article] CCIVR facilitates comprehensive identification of cis-natural antisense transcripts with their structural characteristics and expression profiles2022

    • Author(s)
      Ohhata Tatsuya、Suzuki Maya、Sakai Satoshi、Ota Kosuke、Yokota Hazuki、Uchida Chiharu、Niida Hiroyuki、Kitagawa Masatoshi
    • Journal Title

      Scientific Reports

      Volume: 12 Issue: 1 Pages: 15525-15525

    • DOI

      10.1038/s41598-022-19782-5

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] APOBEC3B expression is promoted by lincNMR collaborating with TGF-β-Smad pathway2022

    • Author(s)
      Ota K, Sakai S, Ohhata T, Suzuki T, Uchida C, Niida H, Kitagawa M.
    • Journal Title

      Carcinogenesis .

      Volume: bgac086 Issue: 1 Pages: 1-14

    • DOI

      10.1093/carcin/bgac086

    • Related Report
      2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells.2021

    • Author(s)
      1.Kim C, Sung S, Kim JS, Lee H, Jung Y, Shin S, Kim E, Seo JJ, Kim J, Kim D, Niida H, Kim VN, Park D, Lee J.
    • Journal Title

      Nat Commun.

      Volume: 12 Issue: 1 Pages: 1097-1097

    • DOI

      10.1038/s41467-021-21341-x

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] HDAC3 is required for XPC recruitment and nucleotide excision repair of DNA damage induced by UV irradiation2020

    • Author(s)
      1.Koji Nishimoto, Hiroyuki Niida, Chiharu Uchida, Tatsuya Ohhata, Kyoko Kitagawa, Akira Motegi, Takafumi Suda, and Masatoshi Kitagawa
    • Journal Title

      Mol. Cancer Res.

      Volume: 18 Issue: 9 Pages: 1367-1378

    • DOI

      10.1158/1541-7786.mcr-20-0214

    • NAID

      120007165672

    • Related Report
      2020 Research-status Report
    • Peer Reviewed
  • [Journal Article] Substitution of Thr572 to Ala in mouse c-Myb attenuates progression of early erythroid differentiation.2020

    • Author(s)
      3.Kitagawa K, Uchida C, Horiguchi R, Ohhata T, Sakai S, Niida H, Yasumoto S, Handa Y, Suzuki M, Hashimoto M, Tazawa T, Yokochi Y, Tsuji M, Kitagawa M.
    • Journal Title

      Sci Rep.

      Volume: 10 Issue: 1 Pages: 14381-14381

    • DOI

      10.1038/s41598-020-71267-5

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Chromatin-remodeling factor BAZ1A/ACF1 targets UV damage sites in an MLL1-dependent manner to facilitate NER2022

    • Author(s)
      丹伊田浩行
    • Organizer
      第81回日本癌学会学術総会
    • Related Report
      2022 Research-status Report
  • [Presentation] Chromatin-remodeling factor BAZ1A/ACF1 targets UV damage sites in an MLL1-dependent manner to facilitate nucleotide excision repair2022

    • Author(s)
      小谷内敬史、丹伊田浩行
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi