CONTROL OF CELL CYCLE EVENTS BY CYCLIN-DEPENDENT KINASES

University Of California Santa Cruz, Santa Cruz CA

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Abstract

The diverse events of the eukaryotic cell cycle are induced and coordinated by the activity of cyclin-dependent kinases, which are activated at specific times during the cell cycle when they associate with members of the cyclin family of proteins. Although much has been learned about the regulation of cyclin-dependent kinase complexes, we still know virtually nothing about the pathways used by these kinases to induce cell cycle events. In simple organisms like budding yeast, a single cyclin-dependent kinase controls all of the events of the cell cycle. It is unknown how cyclin-dependent kinases attain such specificity. One possibility is that the different cyclins serve to determine the functions of specific cyclindependent kinase complexes. The long term goal of this project will be to gain a greater understanding of the pathways used by cyclin-dependent kinases to induce the events of the cell cycle. We will focus on the pathway used by cyclin-dependent kinases in budding yeast to control bud growth during mitosis, since this pathway is particularly amenable to detailed characterization, and preliminary work has already identified one of its components. A combination of genetics and biochemistry will be used to identify additional proteins that function to control bud growth during mitosis, and these will be studied as part of a detailed characterization of the pathway. The control of bud growth is likely to utilize fundamental mechanisms, since several of the proteins known to be involved are highly conserved between humans and yeast. An understanding of the pathways used to execute mitotic events is of considerable clinical relevance, since such pathways are likely to represent good targets for drugs designed to block the division of cancer cells.