Elucidation of regulatory mechanisms of mother-daughter centriole engagement and how defects in this system lead to the associated genetic diseases

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K23718
• 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: The University of Tokyo
• Principal Investigator: Watanabe Koki 東京大学, 大学院薬学系研究科(薬学部), 特任研究員 (70848902)
• Project Period (FY): 2019-08-30 – 2021-03-31
• Keywords: 中心体 / 中心小体間結合 / 中心体複製 / 染色体分配

Outline of Final Research Achievements

The maintenance and loss of centriole engagement is essential for proper centrosome duplication and genome stability, but the mechanisms involved remain poorly understood.
In this study, we found that Cep57 (centrosomal protein 57kDa), the gene responsible for MVA syndrome, and its paralog Cep57L1 inhibit excessive replication of centrioles. In cells in which Cep57 and Cep57L1 expression was suppressed, the daughter centriole was separated from the side of the mother centriole, and a new centriole is formed from each side of the separated centrioles. We also found that, in such situation, the over-duplicated centrioles caused a high frequency of chromosome segregation defects.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

本研究の成果は、中心小体間結合や中心小体複製の回数を制御する機構の新たな生物学的知見であるばかりでなく、中心小体増幅を原因とする癌や遺伝子疾患の発症機構の解明につながることが期待されます。また、これら一連の研究は、がんの治療標的の探索や悪性化の予防といった応用医療に繋がっていくことも期待されます。