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Analysis of S-phase specific replication coupled NER

Research Project

Project/Area Number 16K08580
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field General medical chemistry
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) 2016-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords紫外線 / ヌクレオチド除去修復 / ヒストン / アセチル化 / 脱アセチル化 / HBO1 / HDAC3 / NER / XPC / ヒストンアセチルトランスフェラーゼ / ヒストン脱アセチル化酵素 / メラノーマ細胞 / 細胞周期 / DNA修復 / 癌 / DNA損傷・修復
Outline of Final Research Achievements

We analyzed a novel intracellular factor involved in nucleotide excision repair (NER) that repairs DNA damage after ultraviolet (UV) irradiation. As a result, it was demonstrated that histone acetyltransferase HBO1 acetylates histone H3K14 at the damage site to recruit chromatin remodeling factors of ISWI family and promote accumulation of NER core factors such as XPC. HBO1 phosphorylation in S phase was carried out by ATR that was activated during inhibition of DNA replication. On the other hand, interestingly, it was revealed that the histone deacetylase HDAC3, which deacetylates histone H3K14, also plays a role in recruitment to the damaged site of XPC.

Academic Significance and Societal Importance of the Research Achievements

様々なDNA損傷に働くNER機構が破綻するとメラノーマなど遺伝子変異の多い癌の原因となる。我々の研究から細胞内でNERが正常に働くためにクロマチン構造をオープンにするヒストン修飾と反対にクロマチンをクローズするヒストン修飾両方が必要とされることが示された。この結果はDNA修復過程においてダイナミックな染色体構造の変換が能動的に起こることを意味しており細胞内のNERを理解する一助となる。NERに必要な新たな因子をモニターすることで癌の早期発見など臨床的な応用も可能となる。

Report

(5 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Research-status Report
  • 2017 Research-status Report
  • 2016 Research-status Report

Research Products

(9 results)

All 2020 2019 2018 2017 2016

All Journal Article (3 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 3 results,  Open Access: 3 results) Presentation (6 results) (of which Int'l Joint Research: 1 results,  Invited: 2 results)

  • [Journal Article] Isozyme-Specific Role of SAD-A in Neuronal Migration During Development of Cerebral Cortex.2020

    • Author(s)
      Nakanishi K, Niida H, Tabata H, Ito T, Hori Y, Hattori M, Johmura Y, Yamada C, Ueda T, Takeuchi K, Yamada K, Nagata KI, Wakamatsu N, Kishi M, Pan YA, Ugawa S, Shimada S, Sanes JR, Higashi Y, Nakanishi M.
    • Journal Title

      Cereb Cortex.

      Volume: 160 Pages: 1-14

    • DOI

      10.1093/cercor/bhy253

    • Related Report
      2019 Annual Research Report 2018 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Long Noncoding RNA ELIT-1 Acts as a Smad3 Cofactor to Facilitate TGFβ/Smad Signaling and Promote Epithelial-Mesenchymal Transition.2019

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

      Cancer Res.

      Volume: 79(11) Pages: 2821-2838

    • DOI

      10.1158/0008-5472.can-18-3210

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Phosphorylated HBO1 at UV irradiated sites is essential for nucleotide excision repair2017

    • Author(s)
      Niida, H., Matsunuma, R., Horiguchi, R., Uchida, C., Nakazawa, Y., Motegi, A., Nishimoto, K., Sakai, S., Ohhata, T., Kitagawa, K., Moriwaki, S., Nishitani, H., Ui, A., Ogi, T. and Kitagawa, M.
    • Journal Title

      Nature communication

      Volume: 8 Pages: 1-15

    • DOI

      10.1038/ncomms16102

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] HDAC3 is required for nucleotide excision repair2019

    • Author(s)
      Hiroyuki Niida, Koji Nishimoto, Akira Motegi, Masatoshi Kitagawa
    • Organizer
      第42回日本分子生物学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] HDAC3は転写活性化遺伝子プロモーターからXPCの解離を促しヌクレオチド除去修復を促進する2019

    • Author(s)
      丹伊田浩行、西本幸司、茂木章、北川雅敏
    • Organizer
      日本放射線影響学会第62回大会
    • Related Report
      2019 Annual Research Report
  • [Presentation] Acetylation and deacetylation, both required for nucleotide excision repair2019

    • Author(s)
      Hiroyuki Niida
    • Organizer
      日本核酸医薬学会生物セッション第4回サテライトシンポジウム
    • Related Report
      2019 Annual Research Report
    • Invited
  • [Presentation] Cooperative function of HAT and HDAC facilitate nucleotide excision repair2019

    • Author(s)
      Hiroyuki Niida
    • Organizer
      Gordon Research Conferences 2019 Mammalian DNA Repair
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 紫外線によるDNA損傷修復におけるヒストン修飾の意義2018

    • Author(s)
      丹伊田浩行
    • Organizer
      太陽紫外線防御研究委員会第28回シンポジウム
    • Related Report
      2018 Research-status Report
    • Invited
  • [Presentation] DDB2依存的なHBO1のリクルートはヌクレオチド除去修復に必須である2016

    • Author(s)
      丹伊田浩行
    • Organizer
      第39回日本分子生物学会年会
    • Place of Presentation
      パシフィコ横浜
    • Year and Date
      2016-11-30
    • Related Report
      2016 Research-status Report

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Published: 2016-04-21   Modified: 2021-12-27  

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