Regulation of the Chromosomal Passenger Complex in Mitosis
Banerjee, Budhaditya, Cell Biology - Graduate School of Arts and Sciences, University of Virginia
Stukenberg, Peter, Department of Biochemistry and Molecular Genetics, University of Virginia
The replicated genetic material is equally divided into two daughter cells during mitosis. Aurora B kinase plays a crucial role in achieving error free segregation of chromosomes. It generates the spindle checkpoint signal that ensures each kinetochore has made mature microtubule attachments and triggers pathways that correct erroneous kinetochore attachments. There is evidence that Aurora B kinase activity is regulated directly and also by controlling its localization at centromeres. At the beginning of this thesis work, it was not clear which was the dominant regulatory mechanism. Also, how CPC localizes to centromeres was unclear. This thesis is devoted to understanding the signaling pathways that mediate proper localization of Aurora B and regulation of its kinase activity. In Chapter 1 I will introduce the chromosome passenger complex (CPC) of which Aurora B is the catalytic subunit, its substrates and its overarching role in various mitotic processes. In Chapter 2 I will discuss how three different signaling pathways converge at the inner centromeres to localize Aurora B. In Chapter 3 I will highlight key cofactors that regulate Aurora B activity and elaborate its significance in context of the cell cycle. Finally, Chapter 4 will describe the complexity of Aurora B regulation. I will highlight its role as a control center for integrating signals from a multitude of sources to ensure error free chromosome segregation. I will also discuss some observed but yet unexplored events in mitosis.
PHD (Doctor of Philosophy)
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