Date of Award

2018

Publication Type

Doctoral Thesis

Degree Name

Ph.D.

Department

Biological Sciences

Keywords

APC/C; Cdk; Cell cycle; Cyclins; Meiosis

Supervisor

Swan, Andrew

Rights

info:eu-repo/semantics/openAccess

Abstract

Meiosis is a highly regulated cell division yielding four genetically different gametes. As in mitosis, meiosis is regulated by Cyclin dependent kinases (Cdks). Cdks are activated when bound to their cyclin partners. The type of cyclin bound confers the substrate specificity of the Cdk, but some redundancies exist within cyclin families. In Drosophila, there are three major mitotic cyclins, cyclin A, B, and B3, whose roles in mitosis have been extensively studied, but little has been conducted in meiosis. We first investigated the roles and redundancies of mitotic cyclins in meiosis. We found that cyclin A is the primary mediator of nuclear envelope breakdown (NEB), although all the cyclins can compensate. Cyclin A also plays a role in regulating chromosome bi-orientation. Cyclin B is largely dispensable for meiosis progression, but plays a role in chromosome cohesion. Finally, cyclin B3 is important for anaphase progression. When pairwise knockdowns were performed, cyclin A and B3 showed largely overlapping functions. This was contrary to what was observed in mitosis where cyclin B and B3 shared redundant function. These results indicate that the mitotic cyclins have more distinct roles in meiosis than in mitosis. We then focused on the role of cyclin B3 in anaphase where we found that cyclin B3 promotes APC/CCort and APC/CFzy, to target cyclin B for degradation. Furthermore, we found that the APC/C can recognize a novel motif present in the N-terminus of cyclin B. We also showed that cyclin B3 may function in regulating microtubule dynamics, which appear to be APC/C dependent. These results provide insight into APC/C and anaphase regulation and meiosis progression in Drosophila.

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