Through study of model organisms such as the budding yeast, we have learned a great deal about the mechanisms behind the cell cycle, the basic principles of which are conserved throughout evolution. These insights have led to a great deal of breakthroughs in the medical field; most notably in the understanding of the genetic lesions that lead to human cancer. This proposal focuses on the study of a cell cycle checkpoint in budding yeast, the morphogenesis checkpoint. Budding yeast have the ability to halt their commitment to mitosis if the process of bud formation is disrupted, waiting until a proper bud is formed before proceeding with the cell cycle. Interestingly, this checkpoint uses much of the same cell cycle machinery as the DNA damage checkpoint in humans. Specifically, the budding yeast homologs of the Wee1 kinase and Cdc25 phosphatase are key players in the morphogenesis checkpoint as well. It remains to be determined, however, how these proteins are regulated in checkpoint inducing conditions. The biochemical and genetic studies outlined in this proposal are designed to elucidate these modes of regulation such that a mechanism for cell cycle arrest in response to checkpoint inducing conditions can be understood. These studies could reveal modes of regulation of these important cell cycle control proteins that are conserved in their human homologs.
