Multilateral analysis of the fate of chromosome fusions

2023 Fiscal Year Final Research Report

• Project/Area Number: 20H03183
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 43010:Molecular biology-related
• Research Institution: Kyoto University
• Principal Investigator: Hayashi Makoto 京都大学, 医学研究科, 客員准教授 (90761099)
• Co-Investigator(Kenkyū-buntansha): 加賀谷 勝史 東京大学, 大学院情報理工学系研究科, 特任研究員 (00580177)
• Project Period (FY): 2020-04-01 – 2024-03-31
• Keywords: テロメア / 染色体融合 / 細胞周期 / RECQヘリケース / 自然免疫 / cGAS / STING

Outline of Final Research Achievements

In this study, we analyzed the effects of chromosome fusion on cells. In Project 1, we examined the mitotic telomere deprotection phenomenon during the cell cycle arrest in M phase resulting from fusion, elucidating part of the molecular mechanisms involving the RECQ helicase family factors WRN and BLM. In Project 2, we developed reporter cells to analyze in detail the fate of chromosome fusion and investigated the fate of sister chromatid fusion. As a result, we discovered that micronuclei are generated from fusion. Furthermore, using the reporter cells, we conducted a detailed analysis of the innate immune response due to micronuclei, which had been a widely accepted theory. We made a novel finding that micronuclei are not potent inducer of the cGAS-STING-dependent innate immune response pathway.

Free Research Field

分子細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は，染色体融合が細胞に与える様々な影響の一端についての分子レベルでのメカニズムを明らかにした．これらの知見は，細胞ががん化する過程の理解や，正常な細胞とがん細胞の差異の理解に繋がり，がん治療や遺伝病の新しい治療法開発に貢献する可能性がある．