A Meiosis - Specific Form of the Anaphase Promoting Complex / Cyclosome Regulates the Oocyte - to - Embryo Transition in Drosophila

Cell cycle transitions during mitosis and meiosis must proceed in an irreversible manner. At the heart of this is the Anaphase Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase. The APC/C targets its substrates for degradation, and thus progresses the cell cycle irreversibly forward. Many substrates of the APC/C have been identified in mitosis, but how the APC/C regulates meiosis is less well understood. The Drosophila gene cortex encodes a female, meiosis-specific activator of the APC/C. We set out to identify specific substrates of APCcor both genetically and biochemically. A genetic screen identified five deficiencies that suppress an arrest caused by low APCcot activity. In some cases, these deficiencies could be narrowed to regions containing only a few genes. IP/mass-spectrometry was also performed to identify interactors of Cortex. One hit was Matrimony, a potent inhibitor of Polo kinase during prophase 1. Cort and Mtrm can interact directly in vitro, while a mitotic APC/C activator, fzy/cdc20, cannot. Mtrm proteins levels are drastically reduced upon completion of meiosis, and this reduction is dependent on cort. When expressed in cell culture, Cort causes a proteasome dependent decrease in Matrimony protein levels. Cort and Mtrm also interact genetically, and overexpression of Mtrm in the early embryo causes developmental defects in a subset of embryos. This work contributes to our understanding of the meiotic cell cycle and the specific regulation that distinguishes it from mitosis. Thesis Supervisor: Terry L. Orr-Weaver Title: Professor of Biology