The primary objective of this research proposal is to isolate the fission yeast homolog of human CENP-E, a kinetochore-associated protein involved in the segregation of chromosomes during mitosis. CENP-E is a kinesin- related protein which is thought to act as a motor protein for chromosomes.
The specific aims of this research proposal are to 1.) Isolate fission yeast homolog of CENP-E via DNA hybridization; 2.) Determine if CENP-E is an essential gene, and at what point in mitosis CENP-E is required; and 3.) Identify proteins which interact with CENP-E. The isolation of yeast CENP-E will allow a much needed genetic analysis of this gene and will allow us to answer many fundamental questions which cannot be addressed currently in mammalian systems. A clear understanding of the role of CENP-E, identification of CENP-E associated proteins, and studies of their interactions with the cell cycle machinery will allow the possible development of inhibitory compounds which prevent normal chromosome segregation. By interfering with the ability of the kinetochore to interact with spindle machinery or by interfering with motor activity, such inhibitory compounds could be extremely effective cancer therapeutics, selectively affecting rapidly dividing tumor cells.
