Silencing of the checkpoint allows separation of sister chromatids and cell cycle progression. The exact mechanism by which the checkpoint signal is silenced is not fully understood although it is known that binding of microtubules to CENP-E results in the silencing of BubR1 kinase activity and reduced checkpoint activity. Once each kinetochore is correctly attached to the mitotic spindle, the checkpoint can be switched off. considered various simplified models of how a single unattached kinetochore could generate a diffusive signal that could prevent the onset of anaphase in yeast. Destruction of securin activates the proteolytic enzyme sepharase, which cleaves cohesion allowing separation of sister chromatids. Recently, mathematical modeling of the spindle assembly checkpoint, both in open and closed mitosis, has provided some mechanistic understanding of how the checkpoint could operate (34, 35).Doncic et al. The spindle assembly checkpoint (SAC) ensures correct chromosome segregation by providing time for proper kinetochore (KT) attachment to spindle microtubules (MTs) through inhibition of the anaphase-promoting complex (APC Musacchio and Salmon, 2007). HNSC cell lines treated with nocodazole had mitotic indices. In the ÿpresence of a kinetochore-spindle attachment error the SAC inhibits further progression of the cell cycle and the activity of Aurora B is required at the kinetochore to correct the errors present. Spindle assembly checkpoint intact control cell line HCT 116 exhibited an 85 mitotic index and 73 G2/M fraction, and checkpoint deficient, negative control cell line SW 480 had a 1 mitotic index and a 22 G2/M fraction after 24 hr of nocodazole treatment, as expected (Fig.
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