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

Analyses of the function of Mcmdc2 in DNA repair during meiosis

Research Project

Project/Area Number 21K06159
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 44010:Cell biology-related
Research InstitutionNational Institute of Genetics

Principal Investigator

Sakai Noriyoshi  国立遺伝学研究所, 遺伝形質研究系, 准教授 (50202081)

Project Period (FY) 2021-04-01 – 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: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2022: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2021: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Keywords減数分裂 / Mcmdc2 / ゼブラフィッシュ / mcmdc2 / DNA修復
Outline of Research at the Start

減数分裂期のDNA修復制御機構を解明する目的で、ゼブラフィッシュ減数分裂変異体の原因遺伝子mcmdc2遺伝子の機能解析を行う。Mcmdc2タンパクやその複合体形成が予想されるMcm8タンパク質、Msh4/5タンパク質等の抗体を作製して、ゼブラフィッシュの野生型と変異体において他の減数分裂期DSB修復制御因子との共局在を観察し、組換え修復における相互関係および交叉による修復への関与を調べる。

Outline of Final Research Achievements

Generation and repair of DNA double strand breaks (DSB) during homologous recombination (HR) is a key step in meiosis that promotes proper alignment and segregation of homologous chromosomes; however, the mechanisms underlying this process remain largely unknown. In this study, we identified the causative gene in the zebrafish ENU mutant imo, which exhibits abnormal meiosis, by complementation testing with mcmdc2 knockout. We then analyzed the dynamics of the synaptonemal complex Sycp1 and Sycp3, the DNA recombinase Dmc1, the DSB marker phosphorylated histone H2AX, the DNA repair protein Msh5, and telomere pairing in the mutants. Our results suggest that the formation and stabilization of DSB repair intermediates during HR are not normal in this mutant. We also found that although chromosomal aneuploidy occurred in oocytes, oogenesis progressed.

Academic Significance and Societal Importance of the Research Achievements

Mcmdc2は、ショウジョウバエとマウスにおいてDSB修復に機能する新規因子であることが示唆されているが、その分子機構は未知である。本研究から、ゼブラフィッシュではMcmdc2はDSB修復中間体の形成・安定化に働き、精子形成過程は減数分裂期で停止する一方で、卵母細胞が減数分裂を超えて発達することが示された。この因子が染色体の正常な分配に一義的に働くことが予想される。本研究では、3xFLAG-Stag-mcmdc2系統やMcmdc2の協働制御因子Mcm8の変異体を作出できているため、今後、これらを用いて解析を進めることで、この複合体が染色体分配に果たす役割を解明できると期待される。

Report

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

    (5 results)

All 2023 2021 Other

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

  • [Journal Article] In vitro storage of functional sperm at room temperature in zebrafish and medaka2023

    • Author(s)
      Kazumasa Takemoto, Toshiya Nishimura, Toshihiro Kawasaki, Yukiko Imai, Karine Levy, Neta Hart, Ivan Olaya, Sean M. Burgess, Yaniv M. Elkouby, Minoru Tanaka & Noriyoshi Sakai
    • Journal Title

      zebrafish

      Volume: 20 Issue: 6 Pages: 229-232

    • DOI

      10.1089/zeb.2023.0054

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Meiotic Chromosome Dynamics in Zebrafish2021

    • Author(s)
      Imai Yukiko、Olaya Ivan、Sakai Noriyoshi、Burgess Sean M.
    • Journal Title

      Frontiers in Cell and Developmental Biology

      Volume: 9 Pages: 757445-757445

    • DOI

      10.3389/fcell.2021.757445

    • Related Report
      2021 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] ゼブラフィッシュにおける減数分裂制御因子の雌雄差2023

    • Author(s)
      酒井則良
    • Organizer
      熊本大学発生医学研究所セミナー
    • Related Report
      2023 Annual Research Report
  • [Remarks] 国立遺伝学研究所小型魚類遺伝研究室

    • URL

      https://www.nig.ac.jp/nig/ja/research/organization-top/laboratories/sakai

    • Related Report
      2023 Annual Research Report
  • [Funded Workshop] 2023 NIG Mini Symposium "Fish and Meiosis"2023

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi