Enhancing the repair of oxidative DNA damage with an artificial endonuclease

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K12167
• 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: Nara Medical University
• Principal Investigator: Sugiura Shigeki 奈良県立医科大学, 医学部, 教育教授 (40179130)
• Co-Investigator(Kenkyū-buntansha): 森 俊雄 奈良県立医科大学, 医学部, 研究員 (10115280)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 酸化的DNA損傷 / 修復亢進 / サイクロプリン

Outline of Final Research Achievements

Cyclopurine is believed to be the cause of progressive neurodegeneration in Xeroderma Pigmentosum Group A (XPA). To investigate whether an artificial endonuclease specific to cyclo-dA promotes cyclo-dA repair, we initially attempted to induce sufficient oxidative damage in cultured cells. However, this attempt was unsuccessful.　Next, we proceeded to examine the relationship between neurodegeneration and cyclopurine by performing immunostaining of cyclo-dA on mouse brain tissues. The results revealed that Xpa mice have higher levels of cyclo-dA lesions compared to wild-type mice at 12 and 26 months of age.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

マウスの脳組織におけるサイクロプリンを免疫染色したところ、12ヶ月齢と26ヶ月齢では Xpa マウスの方が多かったことから、色素性乾皮症患者における神経障害発症に酸化的損傷であるサイクロプリンが関与しているとする従来の仮説を強く支持するものである。