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Study on the role of very-long-chain fatty acids in maintaining genome stability

Research Project

Project/Area Number 19K22389
Research Category

Grant-in-Aid for Challenging Research (Exploratory)

Allocation TypeMulti-year Fund
Review Section Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
Research InstitutionOsaka University

Principal Investigator

Hiraoka Yasushi  大阪大学, 生命機能研究科, 教授 (10359078)

Project Period (FY) 2019-06-28 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2020: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2019: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Keywords超長鎖脂肪酸 / 染色体 / ゲノム / 脂肪酸代謝 / 核膜
Outline of Research at the Start

超長鎖脂肪酸(炭素鎖が21以上の脂肪酸)は、長鎖脂肪酸(炭素鎖が11から20)には代替できない重要な働きがある。そのひとつが皮膚の主要な成分であるセラミドを形成して皮膚バリアを形成することである。超長鎖脂肪酸は細胞内においても必須な働きをすると考えられているが、その詳細はわかっていない。真核細胞のゲノムは核膜に覆われており、核膜は生存にとって重要な役割を持つ。我々は、分裂酵母細胞を使った研究から、超長鎖脂肪酸伸長酵素が核膜構造の維持に働く可能性を見いだしたので、超長鎖脂肪酸が核膜の機能を介してゲノムの安定性に与える影響とその仕組みについて研究する。

Outline of Final Research Achievements

Very long-chain fatty acids are fatty acids with more than 21 carbon chains. Despite being present in only a few percent of total fatty acids, very-long-chain fatty acids have important physiological functions that cannot be replaced by long-chain fatty acids. However, their functions within a cell remain unclear. This study aimed to clarify the intracellular function of very-long-chain fatty acids. In particular, our research focused on the function of the very-long-chain fatty acids on the maintenance of the nuclear envelope and chromatin structure. Our study clarified that very long chain fatty acid synthase and its activity play an important role in the formation and maintenance of the nuclear envelope structure, which is required for genomic stability. Furthermore, it clarified that the nuclear envelope protein Lem2 and ER protein Lnp1 is important for maintaining the boundary between the nuclear envelope and the endoplasmic reticulum membrane.

Academic Significance and Societal Importance of the Research Achievements

超長鎖脂肪酸は、総脂肪酸量のわずか数%しか存在しないにもかかわらず、長鎖脂肪酸には代替できない重要な生理的な働きがある。そのひとつが皮膚のバリアー機能である。超長鎖脂肪酸はセラミド(スフィンゴシンと脂肪酸が結合したもの)として皮膚の脂質膜に含まれることが知られている。しかし、細胞内での、超長鎖脂肪酸の局在や機能など多くの問題が謎のままであった。本研究により、皮膚のない生物である分裂酵母でも、超長鎖脂肪酸が存在し、生存に必須の働きをすることが分かった。さらに、その合成酵素は核膜やER膜に存在し、その活性は、核膜構造の維持を通して、ゲノムの安定維持に働くことが分かった。

Report

(3 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • Research Products

    (13 results)

All 2020 2019 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: 6 results) Presentation (5 results) (of which Int'l Joint Research: 4 results,  Invited: 3 results) Remarks (1 results)

  • [Int'l Joint Research] National Health Research Institutes(その他の国・地域 台湾)

    • Related Report
      2020 Annual Research Report
  • [Journal Article] Nuclear Envelope Proteins Modulating the Heterochromatin Formation and Functions in Fission Yeast2020

    • Author(s)
      Hirano Yasuhiro、Asakawa Haruhiko、Sakuno Takeshi、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Cells

      Volume: 9 Issue: 8 Pages: 1908-1908

    • DOI

      10.3390/cells9081908

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Lem2 and Lnp1 maintain the membrane boundary between the nuclear envelope and endoplasmic reticulum2020

    • Author(s)
      Hirano Yasuhiro、Kinugasa Yasuha、Osakada Hiroko、Shindo Tomoko、Kubota Yoshino、Shibata Shinsuke、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Communications Biology

      Volume: 3 Issue: 1 Pages: 276-276

    • DOI

      10.1038/s42003-020-0999-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Phase separation drives pairing of homologous chromosomes2020

    • Author(s)
      Hiraoka Yasushi
    • Journal Title

      Current Genetics

      Volume: 66 Issue: 5 Pages: 881-887

    • DOI

      10.1007/s00294-020-01077-9

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Transient Breakage of the Nucleocytoplasmic Barrier Controls Spore Maturation via Mobilizing the Proteasome Subunit Rpn11 in the Fission Yeast Schizosaccharomyces pombe2020

    • Author(s)
      Yang Hui-Ju、Asakawa Haruhiko、Ohtsuki Chizuru、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Journal of Fungi

      Volume: 6 Issue: 4 Pages: 242-242

    • DOI

      10.3390/jof6040242

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Intracellular ATP levels influence cell fates in Dictyostelium discoideum differentiation2020

    • Author(s)
      Hiraoka Haruka、Nakano Tadashi、Kuwana Satoshi、Fukuzawa Masashi、Hirano Yasuhiro、Ueda Masahiro、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Genes to Cells

      Volume: - Issue: 5 Pages: 312-326

    • DOI

      10.1111/gtc.12763

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Human Ebp1 rescues the synthetic lethal growth of fission yeast cells lacking Cdb4 and Nup1842020

    • Author(s)
      Osemwenkhae Osaretin P.、Sakuno Takeshi、Hirano Yasuhiro、Asakawa Haruhiko、Hayashi‐Takanaka Yoko、Haraguchi Tokuko、Hiraoka Yasushi
    • Journal Title

      Genes to Cells

      Volume: - Issue: 4 Pages: 288-295

    • DOI

      10.1111/gtc.12757

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Nuclear membrane protein and genome stability2020

    • Author(s)
      Yasushi Hiraoka
    • Organizer
      NIH seminar
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Nuclear membrane homeostasis and genome stability2020

    • Author(s)
      Yasushi Hiraoka
    • Organizer
      The Nucleus Science Talks
    • Related Report
      2020 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 非コードRNAタンパク質複合体の液相分離が相同染色体を対合させる2020

    • Author(s)
      平岡泰、丁大橋 、岡正香澄 、中山潤一、原口徳子
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Annual Research Report
    • Invited
  • [Presentation] Lem2 and Lnp1 cooperatively maintain the nuclear membrane integrity through ESCRT-III functions2019

    • Author(s)
      Hirano Y, Kinugasa Y, Osakada H, Shindo T, Kubota Y, Shibata S, Haraguchi T, Hiraoka Y
    • Organizer
      EMBO The International Fission Yeast Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] Very-long-chain fatty acid elongase Elo2 rescues chromosomal defects associated with loss of nuclear membrane protein Lem22019

    • Author(s)
      Kinugasa Y, Hirano Y, Asakawa H, Chikashige Y, Haraguchi T, Hiraoka Y
    • Organizer
      EMBO The International Fission Yeast Meeting 2019
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Remarks] Hiraoka Laboratory, 細胞核ダイナミクス研究室

    • URL

      https://www.fbs.osaka-u.ac.jp/labs/hiraoka/index.html

    • Related Report
      2020 Annual Research Report

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Published: 2019-07-04   Modified: 2022-01-27  

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