The precise replication and segregation of eukaryotic chromosomes during mitotic cell division is undoubtedly a highly complicated process requiring the participation of hundreds of gene products. Our goals are to define as many as possible of the genes involved in mitotic chromosome transmission in Saccharomyces cerevisiae, to locate the chromosomal domains upon which these gene products act, and to determine what role the proteins play. We have developed novel strategies to accomplish these goals by exploiting decreases in the fidelity of chromosome replication or segregation which result from deficient, excess, or abberrant gene product expression. The decrease in fidelity is signalled either by an increase in the rate of chromosome loss or in mitotic recombination. In order to more effectively exploit fidelity changes we will investigate the relationship between DNA damage and mitotic recombination and we will develop minichromosome substrates with which to define the chromosomal domains where gene products function. Mitotic cell division requires rigid integration of the assembly and function of the mitotic spindle, with the replication and segregation of sister chromatids. Our ultimate goal is to understand how these sophisticated biosynthetic and morphogenetic events are coordinated to produce identical sister cells at mitosis and the reduction of chromosome number in meiosis. We will seek to determine the molecular nature of the events that occur at the telomere and centromere of the chromosome in response to the activity of CDC13, 17 and 15 gene products respectively. This information will permit us to determine how the order of gene product function is achieved at particular steps: either by provision of active gene product or by availability of the substrate on the chromosome at the appropriate time and place.
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