Spatial and temporal regulation of mitotic progression by the spindle checkpoint in Drosophila melanogaster

The spindle assembly checkpoint is a cell-cycle surveillance system which ensures the mother cell equally and faithfully separates its replicated DNA contents into two daughter cells before the onset of anaphase. Mad2, BubRl and Cdc20 (Fzy in Drosophila melanogaster) are all kinetochore proteins whi...

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Bibliographic Details
Main Author: Li, Deyu
Published: University of Newcastle Upon Tyne 2008
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Online Access:http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.491836
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Summary:The spindle assembly checkpoint is a cell-cycle surveillance system which ensures the mother cell equally and faithfully separates its replicated DNA contents into two daughter cells before the onset of anaphase. Mad2, BubRl and Cdc20 (Fzy in Drosophila melanogaster) are all kinetochore proteins which dynamically turnover on and off the mitotic kinetochores. It is believed that these proteins are forming a diffusible kinetochore anaphase inhibitory signal for spindle checkpoint function, inhibiting APC/C activity in order to delay the metaphase-anaphase transition (Musacchio and Salmon, 2007). APC/C is an E3 ubiquitin ligase. It ubiquitinates numbers of cell cycle regulating proteins, such as Cyclin B and Securin, and allows them to be targeted by proteasomes for destruction (Peters, 2006). However, the mechanism of the spatial and temporal interaction of these checkpoint proteins (Mad2, BubRl and Cdc20/Fzy) on kinetochores, and how they assemble to form this inhibitory signal remains unclear.