The Redundant Functions of Aurora B and CENPI in the Spindle Assembly Checkpoint

During mitosis, a cell must segregate its duplicated genetic material into two daughter cells. To accomplish this, large mitosis-specific structures called kinetochores form on centromeres and attach to spindle microtubules. Kinetochores then directly harness the depolymerization of microtubules to move chromosomes to opposite poles during anaphase. This process must occur with extremely high fidelity to ensure genetic stability over generations. Failures lead to aneuploidy and apoptosis (cell death), and are hypothesized to contribute to cancer formation. Monitoring these events is a pathway called the spindle assembly checkpoint (SAC), which halts the progress of mitosis until all kinetochores attach to spindle microtubules. In this dissertation I will describe how the mitotic kinase Aurora B and the centromere component CENPI cooperate to localize SAC activity at unattached kinetochores. In Chapter 1 I will provide a brief overview of mitosis, the kinetochore, and the centromere, followed by a more detailed introduction to the SAC. Chapter 2 will describe the conserved roles of Aurora B and CENPI in SAC signaling. In Chapter 3, I will detail how Aurora B and CENPI have redundant roles in localizing SAC components to unattached kinetochores. Chapter 4 concludes with future directions and describes unpublished results pertaining to ongoing projects.