GENETIC CONTROL OF MICROTUBULE DYNAMICS AND FUNCTION

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The broad, long term objectives of this proposal are to understand the molecular mechanisms that regulate microtubule dynamics in the yeast Saccharomyces cerevisiae and how this process controls chromosome behavior during cell division. This proposal will focus on genetic interactions and regulation of the CDC20 gene, a regulator of microtubule disassembly. The Specific Aims of this grant are: 1). To identify proteins that interact with Cdc2Op and genetic interactions with CDC20. 2). To establish novel in vivo and in vitro assays for microtubule dynamics in yeast and apply them to mutants. 3). To determine the mechanism(s) of regulated CDC20 expression and if it is essential for function. 4). To characterize the CDC20 checkpoint and determine how CDC20 function is integrated into the cell cycle. A major amount of the effort will be devoted to isolating and characterizing mutants and cloning the cognate genes. These efforts will lay important groundwork for future experiments. Microtubules are ubiquitous in structure and function in eucaryotic cells and the mechanisms that regulate their dynamic behavior and integrate their function into the cell cycle are of central importance to understanding mitosis and are likely to be evolutionarily conserved.