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The Role of Sumoylation in Regulating the Mitotic Exit Network

Raymond Suhandynata
Appointment Period: 2017-2018, Grant Year: [32]

Raymond Suhandyanata

During my first year as a post-doctoral fellow, I have been studying the small ubiquitin-like modifier (SUMO) and the role it plays in genome maintenance in the budding yeast Saccharomyces cerevisiae. My particular research interests are to investigate SUMO-mediated regulation of the mitotic exit network (MEN) and chromosome segregation. Disruption of either the mitotic exit network or mechanisms that regulate proper chromosome segregation result in aneuploidy a trademark of cancer cells.

My current research project is working on the role of that sumoylation plays in regulating the mitotic exit network. In particular, the SUMO protease Ulp2 has been shown to have an important role in rDNA silencing and maintenance. Biochemical and structural studies performed in our lab demonstrated the precise mechanism by which Ulp2 associates with the rDNA. I am expanding upon this work by investigating the network of sumoylated proteins at the rDNA, which includes the Cdc14 phosphatase, an essential protein required for mitotic exit. I have currently made substantial progress towards the completion of this project, and much of the preliminary data demonstrating how sumoylation regulates the localization of Cdc14 has been acquired. I currently hope to have a completed manuscript on this topic in the following year.

Another project that I am beginning to undertake is the investigation of the SUMO pathway in humans. Given that our lab has grossly identified the targets of the SUMO E3s and SUMO proteases in budding yeast, we are well equipped to identify the targets of the human SUMO machinery. In particular I am planning to investigate the specific substrates of human SENP3 and SENP5, which are the human SUMO proteases that we believe to functionally overlap with budding yeast Ulp2. Given our lab’s considerable experience and success working with Ulp2, I feel that I have considerable support network to undertake this project in an efficient and effective manner.

Understanding these molecular mechanisms in yeast and extrapolating to humans will allow the possibility for cancer therapeutic studies. Ultimately, I hope that this training grant will supplement my post-doctoral training scientifically as it will allow me to investigate the role of the sumoylation in mammals, and ultimately investigate how the SUMO pathway is connected with cancer.

PUBLICATIONS (resulting from this training): 

Ponte de Albuquerque* C, Suhandynata* RT, Carlson CR, Yuan WT, and Zhou H. Dual substrate recognition of the Ulp2 SUMO protease underlies its specificity in the nucleolus. (2018) Journal of Biological Chemistry. In review. *co-first authors