Progression through the mitotic stage of the cell cycle is regulated by several checkpoint mechanisms to ensure equal chromosomal segregation. Abnormalities during mitosis can result in the gain or loss of chromosomes, a condition known as aneuploidy. The ability to proliferate despite abnormal chromosomal copy number is a key hallmark of human cancers, and how cancer cells override cellular checkpoints is a key area of interest. Post-translational protein modifications such as phosphorylation drive mitotic entry and progression, while the ubiquitin-mediated targeting of proteins facilitates exit from mitosis. Here we present the functional requirement of another post-translational modification known as the Small Ubiquitin-related Modifier (SUMO). While the history of SUMO discovery is tied to functions in regulating mitotic progression, here we present a novel role for SUMO modification in regulating the activity of an E3 ubiquitin ligase known as the Anaphase Promoting Complex/Cyclosome during the metaphase-anaphase transition. Further characterization on the SUMO isopeptidase SENP1 during different stages of the cell cycle is also presented herein. Taken together, this thesis provides additional insights to the regulatory roles of how a small protein can have profound effects on cellular function
