Functional analyses of nucleoskeleton proteins on formation of radiation-induced nuclear foci of DNA repair factors

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K18195
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 63020:Radiation influence-related
• Research Institution: Hiroshima University
• Principal Investigator: Horikoshi Yasunori 広島大学, 原爆放射線医科学研究所, 助教 (00719429)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 放射線 / DNA修復 / 細胞核構造 / 核骨格タンパク質

Outline of Final Research Achievements

The functional connectivity between higher-order nuclear architecture and responses to radiation exposure or DNA repair mechanisms of cells has been poorly understood. In this study, we focused NuMA, one of the “nucleoskeleton” proteins, and showed its involvement in both radiation susceptibility and DNA repair. We also revealed that the phosphorylation of NuMA occurs in the early stage of DNA damage responses and then amplified. This modification is limited to the vicinity of damage sites albeit their distribution throughout the entire nucleus. Besides, we found the radiation dose-dependent reduction of NuMA proteins, suggesting the effect of radiation exposure on the higher-order nuclear architecture together with chromosome DNA.

Free Research Field

放射線生物学

Academic Significance and Societal Importance of the Research Achievements

細胞核高次構造と、細胞の放射線応答やDNA修復機構との、機能の関連については、これまで十分には理解されていない。本研究は、ゲノム修復という「核機能」の制御に「核構造」を担う因子が関わっている具体例を示したことで、「構造による機能制御」の新しいモデルの提唱・確立に貢献した。また、放射線被ばくによりDNA以外にも細胞核、特にその高次構造が損傷を受けうるという研究結果は、今後放射線生物学に新たな展開をもたらすものと考えている。放射線治療という観点からも新たな知見であり、将来的な応用が期待される.