The role of nucleoskeleton proteins in DNA damage repair foci formation

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K15017
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: National Institutes of Biomedical Innovation, Health and Nutrition (2022-2023); Hiroshima University (2021)
• Principal Investigator: Kinugasa Yasuha 国立研究開発法人医薬基盤・健康・栄養研究所, 医薬基盤研究所 ヘルス・メディカル微生物研究センター, 研究員 (60852118)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: クロマチン / ラミン / 核構造 / DNA損傷

Outline of Final Research Achievements

In this study, we aimed to elucidate the role of nucleoskeleton proteins in the formation process of DNA repair domains formed by DNA double-strand breaks. We focused on the nucleoskeleton protein Lamin B1 and the homologous recombination repair factor RAD51. Since it was reported that Lamin B1 promotes RAD51 foci formation upon DNA damage, we analyzed the interaction between them. As a result, Lamin B1 interacted with RAD51 in the chromatin fraction, and the interaction was temporary weakened upon DNA damage. These results suggest that Lamin B1 play a role as a scaffold for RAD51 under DNA non-damaged state and loosen the interaction to allow DNA repair foci to form dynamically.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

これまで、核内タンパク質の核膜局在化や核膜直下のクロマチン発現制御など核ラミナにおけるラミンの役割は明らかになりつつあるが、核膜直下以外における機能はあまり知られておらず、核内ドメイン形成への関与は未だ不明な点が多い。本研究結果は、ラミンによる核内ドメイン形成を促進するメカニズムの解明のために重要な知見をもたらすものであり、核骨格タンパク質の新たな役割を提唱するものである。