Suppression of homologous recombination by anti-recombinase

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K06604
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 43050:Genome biology-related
• Research Institution: Kindai University
• Principal Investigator: Matsuzaki Kenichiro 近畿大学, 農学部, 助教 (10772147)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 相同組換え

Outline of Final Research Achievements

Homologous recombination (HR) is essential mechanism to maintain genome stability. Homology search and strand invasion steps in HR are catalyzed by RAD51 protein. Formation of RAD51 filament on ssDNA is necessary to execute proper HR and restart of DNA replication forks, while inappropriate RAD51 filament formation causes genome instability. Hence, RAD51 filament formation is tightly suppressed by anti-recombinases, which promote the dissociation of RAD51. However, the mechanisms underlying genome instability caused by inappropriate RAD51 assembly and the suppression by anti-recombinases remain largely unknown. Here, we report a role for the human AAA+ ATPase, FIGNL1 as a novel anti-recombinase. FIGNL1-deficient cells show the excessive RAD51 recruitment. RAD51 filaments persist and cause defects in chromosome segregation. Our data suggest that recombination intermediates caused by inappropriate RAD51 assembly prevent chromosome segregation and induce genome instability.

Free Research Field

相同組換え

Academic Significance and Societal Importance of the Research Achievements

相同組換えは、DNA二重鎖切断の修復機構であり染色体の安定性を維持する上で重要な経路である。相同組換えが正常に機能しない場合、染色体の不安定化から発がんにつながる。一方で、過剰な相同組換えの活性化も染色体の不安定化を起こす。このことからも、細胞のがん化を防ぐには、相同組換えの制御機構を理解することが重要になってくる。さらに相同組換えの過剰な活性化が、どのように染色体を不安定化しているのか具体的な機構は不明である。本研究では、相同組換えを抑制するAnti-recombinaseの機能解析をとおして、過剰な相同組換えによる発がんのメカニズムの理解を目指す。