Elucidation of the molecular mechanism of the strand transfer reaction in DNA damage tolerance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K12159
• 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: National Cancer Center Japan (2021-2022); Nagoya University (2020)
• Principal Investigator: Matsuo Rika (楠本理加) 国立研究開発法人国立がん研究センター, 研究所, 外来研究員(特別研究員RPD) (90514133)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: UV / 損傷トレランス / 不死化 / MEF / ゲノム不安定性

Outline of Final Research Achievements

DNA damage tolerance (DDT) is a term for reactions that occur to escape DNA replication inhibition caused by DNA damage.Cellular experiments suggested a pathway for DDT via the strand transfer reaction. In this study, we detected this pathway using oligo DNA containing UV damage, cell extracts from xeroderma pigmentosum variant, and a model DNA for sister chromatid. We hypothesize that DDT is involved in the immortalization of primary mouse embryonic fibroblasts (MEFs). We show that UV-C promotes MEF immortalization and that a mixture of polyphenols suppresses immortalization in MEFs.

Free Research Field

DNA修復

Academic Significance and Societal Importance of the Research Achievements

DNA損傷トレランスには未知の経路があると考えられており、そのメカニズムの一端を初めて無細胞系で明らかにしたことは、学術的に意義がある。また、ポリフェノール類がUVによるMEFの不死化促進を抑制したことは、ポリフェノール類によるがん予防の可能性を示唆している。