Cell Cycle Progression
Abstract:Disruption of the orderly progression of cell cycle events often leads to unrestrained cell growth and predisposition to cancer. Research into the molecular mechanisms that regulate these processes is consequently of great medical and scientific interest. In the budding yeast Saccharomyces cerevisiae, DBF4 and CDC7 encode the regulatory and catalytic subunits of the conserved eukaryotic Dbf4-dependent kinase (DDK), respectively. Although levels of Cdc7p remain constant through the cell cycle, Dbf4p is an usntable protien whose levels peak at the onset of S phase and are maintained until late mitosis, after which the protein is ubiquitinated and ultimately proteolyzed. The carefully timed degradation of Dbf4p and other cell cycle-regulated protiens limits DNA replication to once per cycle. We are taking both a genetic and bichemical approach to understand the regulated proteolysis of Dbf4p and selected mitotic protiens in this organism. Current efforts include examining protien-protein interactions amoung chosen mitotic protiens and known regulators of proteolysis, as well as an assessment of the genetic interactions amoung these same regulators.
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