Title:
How cells ensure switch-like chromosome segregation in anaphase

Toru Hirota
Cancer Institute of the Japanese Foundation for Cancer Research (JFCR)

Abstract:
Chromosome segregation is triggered by the cleavage of cohesin complexes that topologically hold sister chromatids. This reaction is specifically mediated by a protease separase, the activity of which must be rigorously suppressed until the right　moment. Two separase-binding proteins have been implicated in inhibiting its activity: securin and cyclin B1. Proteolysis of these separase inhibitors therefore allows separase activation; however, it is well long before the anaphase onset when the　spindle-assembly checkpiont (SAC) brake is released and the anaphase-promoting complex, or cyclosome (APC/C) beginsto degrade securin and cyclin B1. This ‘time lag’ prompted us to investigate spatiotemporal regulation of separase. To address this, we developed a fluorescence-based reporter to probe separase activity, and found that its activity is suppressed for much of metaphase and activated shortly before the anaphase onset. We propose a model by which enables the abrupt separase activation during the metaphase-to-anaphase transition.