Mechanistic studies of double-strand break repair at repeated sequences in the genome

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12328
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Meisei University
• Principal Investigator: Kagawa Wataru 明星大学, 理工学部, 教授 (70415123)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: DNA二重鎖切断修復 / DNA修復経路 / single-strand annealing / 反復配列 / ミスマッチ塩基対 / DNAアニーリング反応 / RAD52

Outline of Final Research Achievements

DNA double-strand break is the most lethal form of DNA damage, and cells have multiple mechanisms to repair it. In the present study, we focused on the molecular mechanism of single-strand annealing (SSA), which repairs double-strand breaks that occur within repetitive sequences of the genome. Using a GFP reporter assay and a biochemical assay, we examined whether mismatch base pairs and altered RAD52 expression levels have an effect on the efficiencies of SSA and DNA annealing. We found that over-expression of RAD52 leads to inaccurate SSA. Furthermore, we found that inaccurate DNA annealing reaction was suppressed in the presence of RPA.

Free Research Field

構造生物学，生化学

Academic Significance and Societal Importance of the Research Achievements

RAD52はがん細胞において過剰発現し，がんの発症と進行に関わっていることが指摘されている。抗がん剤の開発を目的としたRAD52の阻害剤の探索は世界的に行われているが，RAD52の分子レベルでの機能は未だ不明な点が多い。本研究で明らかにしたRAD52による不正確なDNAアニーリング反応は，がん細胞におけるゲノム不安定性と関係している可能性が考えられ，このメカニズムの理解は学術的に意義があるだけでなく，がん治療開発の観点からも意義深い。