DNA double-strand break repair regulated by nuclear bodies

2019 Fiscal Year Final Research Report

• Project/Area Number: 16H05888
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Single-year Grants
• Research Field: Risk sciences of radiation and chemicals
• Research Institution: Ritsumeikan University
• Principal Investigator: Nishi Ryotaro 立命館大学, 生命科学部, 助教 (80446525)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: DNA修復 / 相同組換え修復 / 核内構造体 / Nuclear speckles / ユビキチン化 / 脱ユビキチン化 / R-loop

Outline of Final Research Achievements

The integrity of genomic DNA that is challenged by various endogenous and exogenous sources is maintained by DNA repair mechanisms that remove and repair a wide variety of DNA damages. DNA double-stand breaks (DSBs) are one of the most deleterious type of DNA damage, which can be generated by ionizing radiation. DSBs are mainly repaired by either non-homologous end-joining or homologous recombination repair. In this study, we sought to reveal potential involvement of nuclear bodies in DSB repair. Among these, we focused on nuclear speckles that localize next to transcriptionally active regions. Mechanistically, we established that USP42, hitherto unidentified nuclear speckle factor, promoted homologous recombination repair.

Free Research Field

DNA修復

Academic Significance and Societal Importance of the Research Achievements

本研究では、DSB修復、特に相同組換え修復、への影響を指標に核内構造体であるnuclear specklesを構成するタンパク質をスクリーニングした。その結果、複数の新規因子がDSB修復に正あるいは、負に寄与することが示唆され、nuclear specklesという核内空間の特異的な領域を占める構造体がゲノム安定性に寄与することが明らかになった。これは、核内構造体によって規定されるゲノム構造・機能がDSB修復に重要であることを示唆しており、新しい研究領域を切り開いたものであると言える。