Investigation of the nucleus-endoplasmic reticulum cooperative zone which plays roles in DNA quality control

2021 Fiscal Year Final Research Report

• Project Area: Toward an integrative understanding of functional zones in organelles
• Project/Area Number: 17H06416
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Hiroshima University
• Principal Investigator: Imaizumi Kazunori 広島大学, 医系科学研究科(医), 教授 (90332767)
• Co-Investigator(Kenkyū-buntansha): 金子 雅幸 長崎大学, 医歯薬学総合研究科(薬学系), 教授 (10322827)
• Project Period (FY): 2017-06-30 – 2022-03-31
• Keywords: オルガネラゾーン / 核膜 / DNA損傷 / 小胞体ストレスセンサー

Outline of Final Research Achievements

Endoplasmic reticulum transmembrane transcription factor OASIS is characterized by accumulation at the collapsed nuclear envelope (nuclear-endoplasmic reticulum linkage zone). In this research, we aimed to elucidate the zone structure and the repair mechanism of the collapsed nuclear envelope. As a result, it was found that multiple factors in addition to OASIS are accumulated in the zone, and they cooperatively promote the repair of the nuclear envelope. Oasis itself is not directly involved in its repair, but it has been found to play an important function in creating a repair environment by suppressing the cell cycle. Furthermore, in glioblastoma, we found that the OASIS gene promoter region received DNA methylation, and succeeded in developing a method to stop the growth of cancer cells by inducing DNA demethylation by epigenome editing.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

これまで未解明であった核膜損傷に対する修復システムの一端が解明できたことは、核膜損傷によって生じる様々な核機能障害の理解につながり、細胞核研究領域の新分野創成に発展することが期待できる。さらに核膜損傷が引き金となって発症する核膜病やがん転移の予防あるいは治療する新技術開発に向けた研究基盤となることから社会的にも意義深い成果と考えられる。