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Investigating the mechanisms of crossover recombination duiring meiosis

Research Project

Project/Area Number 20K15716
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 43010:Molecular biology-related
Research InstitutionOsaka University

Principal Investigator

Ito Masaru  大阪大学, 蛋白質研究所, 助教 (30869061)

Project Period (FY) 2020-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2023: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Keywords減数分裂組換え / 配偶子形成 / 相同組換え / DNA修復 / 生殖細胞 / 減数分裂 / 交叉型組換え / 組換えDNA合成
Outline of Research at the Start

マウスやヒトなどの哺乳細胞では、DNA二本鎖切断によって開始された減数分裂組換えの内、10%程度しか交叉型組換えを起こさない。第一減数分裂における正常な染色体分配を保証するために、各相同染色体対当たり必ず1箇所は交叉型組換えが起こるように厳密に制御されているが、その仕組みは詳しくはわかっていない。本申請研究では、減数分裂組換えに伴うDNA合成に着目することで、交叉型組換えの選択がいつ、どのように起こるのか、DNAレベルで検証する。具体的には、 組換えDNA合成の経時的かつゲノムワイドなマッピング法を確立し、変異体マウスを用いて解析することで、交叉型組換え選択の制御機構を明らかにする。

Outline of Final Research Achievements

I generated several mutant mice and analyzed phenotypes in meiosis, particularly in meiotic recombination. Among them, a germ-line specific conditional knockout (cKO) of Fignl1 resulted in defective synapsis of homologous chromosomes and crossing over. RAD51, a central player of meiotic recombination, was accumulated on chromosomes in not only early meiotic prophase I where meiotic recombination takes place but also in pre-meiotic S-phase in Fignl1 cKO spermatocytes. Importantly,RAD51 accumulation was also seen in Spo11 KO Fignl1 cKO spermatocytes where DNA double-strand breaks that initiate meiotic recombination do not occur. This suggests that RAD51 removal from both single-stranded DNA at the sites of meiotic recombination and intact double-stranded DNA is critical for meiotic recombination and fertility.

Academic Significance and Societal Importance of the Research Achievements

減数分裂組換えの破綻は不妊症やダウン症等の疾患の一因であることが知られており、FIGNL1はヒトの早期卵巣不全の原因遺伝子としても報告されている。従って、本研究により明らかになったFIGNL1の機能は、将来的な生殖補助医療や不妊治療へと繋がることが期待される。また、相同組換えは体中の細胞で生じるDNA損傷の修復に必須であり、相同組換えの破綻が細胞のがん化を引き起こすことも知られている。FIGNL1は体細胞でも発現していることから、本研究で明らかにした、RAD51のDNAからの解離を解した相同組換え制御の仕組みの理解は、将来的ながん予防やがん治療へと繋がることが想定される。

Report

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

    (19 results)

All 2024 2023 2022 2021 2020

All Journal Article (8 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 6 results,  Open Access: 4 results) Presentation (11 results) (of which Int'l Joint Research: 2 results,  Invited: 2 results)

  • [Journal Article] Positive and negative regulators of RAD51/DMC1 in homologous recombination and DNA replication2024

    • Author(s)
      Ito Masaru、Fujita Yurika、Shinohara Akira
    • Journal Title

      DNA Repair

      Volume: 134 Pages: 103613-103613

    • DOI

      10.1016/j.dnarep.2023.103613

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed
  • [Journal Article] FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in pre-meiotic DNA replication and meiotic recombination2023

    • Author(s)
      Ito Masaru、Furukohri Asako、Matsuzaki Kenichiro、Fujita Yurika、Toyoda Atsushi、Shinohara Akira
    • Journal Title

      Nature Communications

      Volume: 14 Issue: 1 Pages: 6857-6857

    • DOI

      10.1038/s41467-023-42576-w

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] DNA double‐strand breaks regulate the cleavage‐independent release of Rec8‐cohesin during yeast meiosis2023

    • Author(s)
      Fajish Ghanim、Challa Kiran、Salim Sagar、VP Ajith、Mwaniki Stephen、Zhang Ruihao、Fujita Yurika、Ito Masaru、Nishant Koodali T.、Shinohara Akira
    • Journal Title

      Genes to Cells

      Volume: 29 Issue: 1 Pages: 86-98

    • DOI

      10.1111/gtc.13081

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments in meiotic DNA replication and recombination2023

    • Author(s)
      Masaru Ito, Asako Furukohri, Kenichiro Matsuzaki, Yurika Fujita, Atsushi Toyoda, Akira Shinohara
    • Journal Title

      bioRxiv

      Volume: ND

    • DOI

      10.1101/2023.03.26.534288

    • Related Report
      2022 Research-status Report
    • Open Access
  • [Journal Article] SUMO is a pervasive regulator of meiosis2021

    • Author(s)
      Bhagwat Nikhil R、Owens Shannon N、Ito Masaru、Boinapalli Jay V、Poa Philip、Ditzel Alexander、Kopparapu Srujan、Mahalawat Meghan、Davies Owen Richard、Collins Sean R、Johnson Jeffrey R、Krogan Nevan J、Hunter Neil
    • Journal Title

      eLife

      Volume: 10

    • DOI

      10.7554/elife.57720

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Proline-rich protein PRR19 functions with cyclin-like CNTD1 to promote meiotic crossing over in mouse2020

    • Author(s)
      Bondarieva A、Raveendran K、Telychko V、Rao H. B. D. P、Ravindranathan R、Zorzompokou C、Finsterbusch F、Dereli I、Papanikos F、Trankner D、Schleiffer A、Fei J、Klimova A、Ito M、Kulkarni D S.、Roeder I、Hunter N、Toth A
    • Journal Title

      Nature Communications

      Volume: 11 Issue: 1

    • DOI

      10.1038/s41467-020-16885-3

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] PCNA activates the MutLγ endonuclease to promote meiotic crossing over2020

    • Author(s)
      Kulkarni Dhananjaya S.、Owens Shannon N.、Honda Masayoshi、Ito Masaru、Yang Ye、Corrigan Mary W.、Chen Lan、Quan Aric L.、Hunter Neil
    • Journal Title

      Nature

      Volume: 586 Issue: 7830 Pages: 623-627

    • DOI

      10.1038/s41586-020-2645-6

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Cytological Monitoring of Meiotic Crossovers in Spermatocytes and Oocytes2020

    • Author(s)
      Yun Yan、Ito Masaru、Sandhu Sumit、Hunter Neil
    • Journal Title

      Methods in Molecular Biology

      Volume: 2153 Pages: 267-286

    • DOI

      10.1007/978-1-0716-0644-5_19

    • ISBN
      9781071606438, 9781071606445
    • Related Report
      2020 Research-status Report
    • Int'l Joint Research
  • [Presentation] アンチリコンビナーゼ FIGNL1 による減数分裂期相同組換え制御2023

    • Author(s)
      伊藤将
    • Organizer
      第50回日本毒性学会学術年会
    • Related Report
      2023 Annual Research Report
  • [Presentation] RAD51/DMC1 を介した制御により明らかになる減数分裂組換え制御の性差2023

    • Author(s)
      伊藤将、篠原彰
    • Organizer
      第27回DNA複製・組換え・修復ワークショップ
    • Related Report
      2023 Annual Research Report
  • [Presentation] FIGNL1 AAA+ ATPase remodels RAD51 and DMC1 filaments during pre-meiotic DNA replication and meiotic recombination2023

    • Author(s)
      Masaru Ito
    • Organizer
      MAYosis 2023
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 伊藤 将、松嵜 健一郎、篠原 彰2023

    • Author(s)
      Anti-recombinase FIGNL1による減数分裂組換え制御
    • Organizer
      第3回有性生殖研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] FIGNL1-dependent removal of recombinases is essential for homologous recombination in male meiosis2022

    • Author(s)
      伊藤 将
    • Organizer
      2022 遺伝研研究会 有性生殖における染色体・クロマチン・核動態に関する若手研究者の会
    • Related Report
      2022 Research-status Report
    • Invited
  • [Presentation] FIGNL1-dependent removal of recombinases is essential for homologous recombination in male meiosis2022

    • Author(s)
      Masaru Ito, Ken-ichiro Matsuzaki and Akira Shinohara
    • Organizer
      Gordon Research Conference on meiosis
    • Related Report
      2022 Research-status Report
    • Int'l Joint Research
  • [Presentation] FIGNL1-dependent removal of recombinases is essential for proper homologous recombination in mammalian meiosis2022

    • Author(s)
      Masaru Ito, Ken-ichiro Matsuzaki and Akira Shinohara
    • Organizer
      第45回日本分子生物学会年会
    • Related Report
      2022 Research-status Report
  • [Presentation] 正の制御因子と負の制御因子を介した減数分裂組換え制御2022

    • Author(s)
      伊藤 将、篠原 彰
    • Organizer
      第40回染色体ワークショップ・第21回核ダイナミクス研究会
    • Related Report
      2022 Research-status Report
  • [Presentation] アンチリコンビナーゼによる減数分裂組換え制御2021

    • Author(s)
      伊藤 将、松嵜 健一郎、篠原 彰
    • Organizer
      第26回 DNA複製・組換え・修復ワークショップ
    • Related Report
      2021 Research-status Report
  • [Presentation] Anti-recombinase FIGNL1による減数分裂組換え制御2021

    • Author(s)
      伊藤 将、松嵜 健一郎、篠原 彰
    • Organizer
      第39回 染色体ワークショップ・第19回 核ダイナミクス研究会
    • Related Report
      2021 Research-status Report
  • [Presentation] RING型E3リガーゼRNF212Bによる減数分裂期交叉型組換え制御2020

    • Author(s)
      伊藤 将
    • Organizer
      第43回日本分子生物学会年会
    • Related Report
      2020 Research-status Report
    • Invited

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

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