Grant: Doctoral Research Award: Canada Graduate Scholarships

Eukaryotic cells divide in the highly regulated process called mitosis. One of the most regulated aspects of mitosis is the breaking apart and reformation of the membrane that encloses the nucleus: the nuclear envelope (NE). Decades of research have worked out in great molecular detail how the first step (breaking apart) works, but our understanding of the second half (reformation) is comparatively lacking. Addressing this deficit is important because errors in this process can have catastrophic consequences for genome stability, including the development of cancer and other diseases such as certain muscular dystrophies. Using budding yeast, a model organism where the mechanisms behind nuclear division are similar to humans, we recently discovered that during late mitosis, certain proteins of the NE can be conjugated to the ubiquitin-like post-translational modification SUMO. SUMO is known to often work as a "molecular glue" to stabilize protein complexes, and we hypothesize that this "glue" function of SUMO is relevant to NE reformation. Indeed, blocking NE SUMOylation hinders the cell's ability to properly complete events involved in completing nuclear division. However, although the importance of NE SUMOylation is clear, any mechanistic insights are severely limited by the incomplete cataloguing of which NE proteins are targeted and how SUMO affects their activities. To address this problem, I used state-of-the-art proteomics tools to identify many NE proteins that are SUMOylated specifically in mitosis. I will now assess the impact of SUMOylation on the functions of these proteins and how that controls NE processes relevant to mitosis. Better understanding the role of SUMO in mitosis and how it shapes the NE will provide us with new insights into the underlying processes that are required for cell division, and thus a greater understanding of the mechanistic basis for linked diseases.