One of the fundamental questions of cell biology is how eukaryotic cell division is regulated. A thorough knowledge of this process is the first step in elucidating how cancer cells overcome the normal constraints on proliferation and will suggest points in the cell division process where intervention would be most effective. Knowledge of this process will also improve our understanding of basic biological processes such as development and differentiation. In the last decade, key regulatory elements of the eukaryotic cell cycle have been identified. They are a family of protein-serine/threonine kinases, the cyclin dependent kinases or CDKs. The first of these to be identified was Cdc2. It is now established that the activation of Cdc2 in all eukaryotes triggers the events of mitosis which include chromosome condensation and segregation, nuclear envelope breakdown, and formation and elongation of the mitotic spindle. The eventual inactivation of Cdc2 must occur in order for cells to re-enter a new cell cycle. To ensure the proper coordination between entry into mitosis and completion of other events in the cell cycle, Cdc2 activation is tightly regulated by a large network of gene products which has been conserved throughout evolution. Our project proposes to determine how two other essential highly conserved proteins, termed cdc5p and dim1p, act in G2 in the yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Study of cell cycle control in these organisms has been particularly fruitful for establishing regulatory paradigms applicable to all eukaryotes. Preliminary evidence indicates that cdc5p is involved in pre-mRNA splicing as well as cell cycle control and that dim1p is involved in ubiquitin-mediated degradation. Our long-term goal is to understand how the pathways in which cdc5p and dim1p function are coordinated with known elements regulating entry into mitosis.
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