Repair mechanism for DNA double strand breaks caused by heavy-ion irradiation in quiescent mammalian cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 18K07775
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 52040:Radiological sciences-related
• Research Institution: Institute of Physical and Chemical Research
• Principal Investigator: Izumi Masako 国立研究開発法人理化学研究所, 仁科加速器科学研究センター, 専任研究員 (00280719)
• Project Period (FY): 2018-04-01 – 2022-03-31
• Keywords: DNA修復 / 重粒子線

Outline of Final Research Achievements

Among DNA damages caused by ionizing radiation, DNA double strand breaks (DSBs) are the most lethal damage. Mammalian cells have four pathways to repair DSBs: non-homologs end joining (NHEJ), homologous recombination (HR), alternative non-homologous end joining (a-NHEJ), and single strand annealing (SSA). In mammalian cells, HR plays more important roles in the repair of DSBs caused by heavy-ions. However, a major part of cells in the body or cancer stem cells are in quiescent state (G0) where HR does not work. In this research, it is shown that NHEJ is the major repair pathway in quiescent cells, whereas several essential proteins for a-NHEJ or SSA are not expressed in quiescent cells. On the other hand, several proteins involved in SSA, which is a more error-prone pathway than NHEJ, are recruited to DSBs in G1 cells where HR does not work. Therefore, the repair pathways for DSBs caused by heavy-ions are different between G0 and G1 cells.

Free Research Field

放射線生物学

Academic Significance and Societal Importance of the Research Achievements

重粒子線は先進的ながん治療法として利用されているが、重粒子線に固有のDNA損傷の修復反応は、完全に解明されていない。本研究では静止期の哺乳類細胞における重粒子線照射後のDNA二本鎖切断修復機構を分子レベルで解明するとともに、その結果引き起こされる染色体異常や突然変異のリスクを評価し、二次発がんの危険性を予測し治療最適化のための基盤データとする。また、本研究の成果は宇宙空間における有人飛行の放射線リスク評価にも寄与する。