| Budget Amount *help |
¥18,200,000 (Direct Cost: ¥14,000,000、Indirect Cost: ¥4,200,000)
Fiscal Year 2014: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2013: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2012: ¥7,020,000 (Direct Cost: ¥5,400,000、Indirect Cost: ¥1,620,000)
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| Outline of Final Research Achievements |
The two key events underlying chromosome segregation are the removal of cohesion between sister chromatids and the subsequent poleward movement of disjoined sisters. How cells coordinate these two processes is not well understood. We aimed to address this question, by setting out a probe for separase activity in living cells. Our probe found that separase undergoes an abrupt activation shortly before anaphase onset, specifically in the vicinity of chromosomes. This activation profile depends on securin, to inhibit separase's protease activity and target it to chromosomes. We surprisingly found that, subsequent to its proteolytic activation, separase then binds to and inhibits a subsert of cyclin B1-Cdk1, which antagonizes Cdk1-mediated phosphorylation on chromosomes and facilitates poleward movement of sisters in anaphase. Therefore, separase coordinates two key processes to achieve simultaneous and abrupt separation of sister chromatids.
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