Molecular mechanisms of control of recombination by dynamics of RAD51/DMC1-DNA complexes

2021 Fiscal Year Final Research Report

• Project/Area Number: 19H00981
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Medium-sized Section 43:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Shinohara Akira 大阪大学, 蛋白質研究所, 教授 (00252578)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 相同組換え / ゲノム安定化 / 減数分裂 / DNA２重鎖切断修復 / RAD51

Outline of Final Research Achievements

Homologous recombination is essential for the maintenance of genome stability and creation of genome diversity. RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the homology search and strand exchange in the recombination. The formation of the RAD51 filament is promoted by various positive factors and regulated by negative regulators. However, the mechanisms of control of RAD51 filament dynamics by these factors remain largely unknown. In this study, we report a new role of the human FIGNL1, AAA+ ATPase, as a novel regulator of RAD51 assembly/disassembly. Persistent RAD51 assembly in FIGNL1-depleted human cells suggests its role in the disassembly of RAD51 filaments as a negative regulator. Fignl1 conditional knock-out shows defective meiotic recombination, indicating a positive role in the recombination. Taken together, our data suggest that FIGNL1 plays dual roles in RAD51-filament formation.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は相同組換えのブレーキ役のタンパク質・遺伝子(FIGNL1)の新しい機能を愛からにしました。この因子を生殖細胞で失うと、配偶子を形成できなくなります。このタンパク質の機能を明らかにすることで、生体内でのDNA同士の交換反応である相同組換えを適切に制御する新しいメカニズムを解明しました。相同組換えの機能不全による不妊や異数体病の原因解明や診断・治療方法の開発につながることが期待できます。また、今回発見した組換え因子を人工的に制御することで、ゲノム編集の最適化など幅広い応用が可能であると考えられます。