Date of Award
Doctor of Philosophy
Biochemistry and Cellular and Molecular Biology
Joshua N. Bembenek
Mariano Labrador, Jaan Mannik, Bruce D. McKee, Andreas Nebenführ
Faithful cell division is required to maintain ploidy and generate daughter cells with necessary genetic components for life. During mitosis, dividing cells face the challenge of coordinating multiple processes to ensure that nascent daughter cells inherit an exact copy of the parent cell’s genetic identity to maintain viability. To ensure the proper execution of cell division, multiple core cell cycle proteins, such as Aurora B kinase and separase, are involved in regulating chromosome segregation, cytokinesis and abscission. Interestingly, fundamental roles for these core cell cycle proteins are being characterized in this coordination. Separase regulates chromosome segregation and vesicle trafficking during meiotic and mitotic divisions. Aurora B kinase is well characterized to eliminate incorrect attachments of kinetochore with centromere through its phosphorylation. These faultless attachments initiate a series of signaling pathways to activate separase and promote chromosome segregation. Additionally, Aurora B kinase also phosphorylates centralspindlin to complete cytokinesis and midbody formation. The collection of work presented here addresses the role of these two master cell cycle regulators in cytokinesis, abscission, and cellular events during later morphogenesis. Chapter I outlines the contribution of separase to cytokinesis, highlight how the protease activity of separase regulates exocytosis in anaphase, and suggesting that an unknown substrate is involved in separase’s regulation of exocytosis. Chapter II elucidates how programmed cytokinesis in different tissues contributes to later cellular events during morphogenesis and uncovers the novel migration pattern of midbody to apical surface. Finally, in Chapter III, we present several live imaging methods for observing C. elegans embryogenesis which were applied for this study. Collectively, the work presented here addresses the roles of these master cell cycle regulators in exocytosis, cytokinesis, abscission, and later developmental events, which is critical to understand how failure of cell division promote tumorigenesis and aneuploidy. Finally, our study may provide insightful ideas to generate clinical technologies to cure human infertility, cancer and other genetic diseases.
Bai, Xiaofei, "Investigating the Roles of Master Cell Cycle Regulators during Cytokinesis and Embryonic Development in Caenorhabditis elegans. " PhD diss., University of Tennessee, 2018.