The spindle assembly checkpoint

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The spindle assembly checkpoint Gianluca Varetti, Andrea Musacchio  Current Biology  Volume 18, Issue 14, Pages R591-R595 (July 2008) DOI: 10.1016/j.cub.2008.06.012 Copyright © 2008 Elsevier Ltd Terms and Conditions

Figure 1 The SAC as a synchronization device. (A) A schematic view of the sequential phases of mitosis (see text for a detailed description). Prometaphase starts after nuclear envelope breakdown (time zero) and several unattached sister kinetochores (red dots on blue chromosomes) emit a ‘wait!’ signal that arrests cells in mitosis. The ‘Wait!’ signal is created by the SAC and it targets the APC/C. Biochemically, this allows Cdk1–cyclin B to remain active and separase to remain inactive (the latter through securin-mediated inhibition). The cell shown in this series quickly manages to align its chromosomes at the metaphase plate. All sister kinetochores are now attached (yellow dots) to thick kinetochore fibers (thick black lines). This condition satisfies the SAC. At this point the APC/C becomes activated, cyclin B and securin are polyubiquitylated and destroyed by the proteasome, Cdk1 is inactivated, separase is activated, and anaphase can commence, followed by mitotic exit. (B) A series of events similar to that shown in (A), but, in this case, a couple of chromosomes fail to attach and continue to emit the ‘Wait!’ signal. More time elapses than that in (A), but, because the stability of cyclin B and securin is tuned on the ‘Wait!’ signal, these proteins are stabilized for the time required to achieve metaphase. After metaphase, the two cells follow the same path. Current Biology 2008 18, R591-R595DOI: (10.1016/j.cub.2008.06.012) Copyright © 2008 Elsevier Ltd Terms and Conditions