Investigating the mechanisms of crossover recombination duiring meiosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 20K15716
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Osaka 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
• 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

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.

Free Research Field

分子遺伝学

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。