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Figure 2.
Silencing of the checkpoint acts both in the cytoplasm (a) and locally at each kinetochore (b) upon microtubule attachment.
At a single kinetochore, the binding of the microtubule and subsequent recruitment and activation of protein phosphatase 1 (PP1) locally reduce checkpoint kinase activity and release checkpoint complexes via dissociation of Mad1/Mad2 or translocation along microtubules via dynein. Loss of the single generators culminates in the total loss of generation when all chromosomes become attached. The remaining cytoplasmic inhibitory complexes (MCC-APC/C) are dissociated in part by the natural decay in the absence of generation and also by the activation of pathways that enhance dissociation to produce the synchronous onset of anaphase. The dissociation activity results in the activation of the APC/C by Cdc20, the ubiquitination and degradation of cyclin B and securin, and the onset of anaphase. APC/C, anaphase-promoting complex/cyclosome; AurB, Aurora B kinase; KNL1, kinetochore-null 1; Mad, mitotic arrest defective; MCC, mitotic checkpoint complex; Mps1, monopolar spindle 1; RZZ, rough deal, zeste white 10, zwilch. |
