The molecular mechanisms of the kinetochore assembly during mitosis

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20630
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0701:Biology at molecular to cellular levels, and related fields
• Research Institution: Osaka University
• Principal Investigator: Takenoshita Yusuke 大阪大学, 大学院生命機能研究科, 特任研究員(常勤) (40962965)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 染色体分配 / キネトコア / セントロメア

Outline of Final Research Achievements

During cell division, it is crucial to accurately separate chromosomes to transmit the genetic information to the progeny. This study focuses on the kinetochore, a large protein complex essential for chromosome segregation, and elucidates its assembly mechanism to shed light on the molecular mechanisms underlying accurate chromosome segregation. Specifically, we investigated how the interaction between CENP-T, a component of the kinetochore, and Mis12C, which binds to CENP-T only during chromosome segregation, is regulated. Using a combination of structural biology and cell biology analyses, we found that these interactions are doubly regulated by protein phosphorylation, thereby maintaining the robustness of chromosome segregation.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

細胞分裂の際には染色体を等しく分配する必要があり、染色体分配のエラーにより染色体の数や構造に異常が生じると胎生致死や細胞のがん化などが引き起こされる。このことから、染色体分配の分子機構を理解することは、医学・生物学の重要な課題であるといえる。本研究では、染色体分配に重要なタンパク質複合体キネトコアがどのように形成されるのかを明らかにすることで、遺伝情報が次世代に正確に伝える分子メカニズムについて重要な知見を得ることができた。