Study of the mechanism of regulation of circular chromosome stability conserved in yeast and human

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K07502
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Genetics/Chromosome dynamics
• Research Institution: Hiroshima University
• Principal Investigator: Ueno Masaru 広島大学, 統合生命科学研究科(先), 准教授 (90293597)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: テロメア / 分裂酵母 / ヒト細胞 / 環状染色体 / 抗癌剤

Outline of Final Research Achievements

Ring chromosomes have association with some genetic disorders and cancers. In Schizosaccharomyces pombe, lack of Pot1 results in survivors with circular chromosomes. Therefore pot1 disruptant is suitable to study how cells with circular chromosomes survive and how circular chromosomes are maintained. Fission yeast Cut17/Bir1, Ark1, Pic1, and Nbl1 is a conserved chromosome passenger complex (CPC) functioning mainly throughout mitosis. We found that CPC is synthetically lethal in combination with pot1. We also obtained a novel pik1 mutant, pik1-1, which is synthetically lethal with pot1. We found that pik1-1 mutation does not affect chromosome circularization. Thus, our results suggest that pik1 is required for the maintenance of circular chromosomes. We also found that strains with circular chromosomes, due to loss of pot1,require the 9-1-1 complex for their growth in the presence of DNA replication inhibitor.

Free Research Field

分子生物学

Academic Significance and Societal Importance of the Research Achievements

本研究で見つかった分裂酵母の環状染色体の維持に関与する因子は、ヒトでも同様の機能があることが期待できる。その場合、本研究の成果を利用すると、a)環状染色体を安定化することで、環状染色体を持つ遺伝病患者のがんのリスクを軽減したり、b)環状染色体を不安定化することで、環状染色体を持つがん細胞を選択的に死滅させる新しい抗がん剤の開発につながる可能性があり、がんの予防や治療への貢献が期待できる。