Molecular mechanism of partner choice for recombination by two RecA homologs

2018 Fiscal Year Final Research Report

• Project/Area Number: 16H04742
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Molecular biology
• Research Institution: Osaka University
• Principal Investigator: Shinohara Akira 大阪大学, 蛋白質研究所, 教授 (00252578)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 相同組換え / RAD51 / 減数分裂

Outline of Final Research Achievements

Homologous recombination is essential for the maintenance of genome stability. RAD51 assembly on single-stranded (ss)DNAs is a crucial step in the recombination-dependent repair of DNA damage. The formation of the RAD51 filament is promoted by various RAD51-interacting proteins including RAD51 paralogues. However, the mechanisms underlying the differential control of RAD51 filament dynamics by these factors remain largely unknown. In this study, we report a new role for the human RAD51 paralog, SWSAP1, as a novel regulator of RAD51 assembly and disassembly. Swsap1-deficient cells show defects in DNA damage-induced RAD51 assembly during both mitosis and meiosis. Defective RAD51 assembly in SWSAP1-depleted cells is suppressed by the depletion of FIGNL1, which binds to RAD51 as well as SWSAP1. Purified FIGNL1 promotes the dissociation of RAD51 from ssDNAs. Taken together, our data suggest that SWSAP1 protects RAD51 filaments by antagonizing the anti-recombinase, FIGNL1.

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アクセル役のSWSAP1と連携して機能する、ブレーキ役の新規タンパク質・遺伝子タンパク質・遺伝子(FIGNL1)を発見しました。SWSAP1, FIGNL1の2者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発ガン率の上昇の原因解明や診断・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技術の開発を通して、不妊の治療、ゲノム編集を介した遺伝子治療（置き換え）の最適化など幅広い貢献が期待できます。