Understanding chromosome segregation using Separase biosensor

2017 Fiscal Year Final Research Report

• Project/Area Number: 25711003
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Molecular biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: Shindo Norihisa 公益財団法人がん研究会, がん研究所 実験病理部, 研究員 (00512253)
• Project Period (FY): 2013-04-01 – 2018-03-31
• Keywords: 染色体分離 / 細胞分裂 / セパレース / がん細胞株

Outline of Final Research Achievements

Separase autocleavage was required for its sharp activation during mitosis. We found that instead of promoting separase activation, autocleavage maintained separase in inactive state until the onset of anaphase, by regulating binding of its inhibitor cyclin B1. This tight regulation of separase was widely abrogated in many cancer cell lines, which was highly correlated with longer mitosis. Treating RPE1-a widely used normal diploid cell line, with a low dose of nocodazole, prolonged mitosis and resulted in perturbed tight regulation of separase and frequent chromosome missegregation. Longer mitosis and subsequent deregulation of separase could provide explanation for the frequent chromosome missegregation in cancer cells.

Free Research Field

細胞生物学