Chromosome segregation requires the formation of a microtubule network that connects the spindle poles located at either end of the cell, originating in centrosomes, with kinetochores (protein structures located at the centromeres of each chromosome) ( 4). Failure to do so correctly may lead to genomic instability, aneuploidy, and cancer ( 1– 3). The faithful separation of chromosomes prior to cell division at mitosis is essential for maintaining genomic integrity. Therefore, experimental verification of the results discussed here could provide a deeper understanding of how kinetochores and Aurora B cooperate in the spindle assembly checkpoint. This level of inhibitor concentrations has not yet been studied experimentally, to the authors' best knowledge. Furthermore, when Aurora B inhibition is considered within the model, for a certain range of inhibitor concentrations, a prolonged prometaphase/metaphase is observed. We find that the current model of the spindle assembly checkpoint is robust to variation in its key diffusion-limited parameters. Here, we use mathematical modeling to extend a current model of the spindle assembly checkpoint to incorporate all signaling kinetochores within a cell rather than just one and the role of Aurora B within the resulting model. Aurora B is overexpressed in a subset of cancers and is required for mitosis, making it an attractive anticancer target. Aurora B plays a role in the spindle assembly checkpoint, in part, by destabilizing the localization of BubR1 and Mad2 at centrosomes and responds to changes in tension caused by aberrant microtubule kinetochore attachments. One family of serine/threonine kinases that plays a central role in regulation is the Aurora family. Faithful separation of chromosomes prior to cell division at mitosis is a highly regulated process.
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