The meiotic cell cycle enables diploid organisms to generate haploid gametes by completing a single round of DNA replication followed by two successive rounds of chromosome segregation. Therefore, the faithful transmission of genetic information at meiosis is essential for the propagation of sexually reproductive organisms. Missegregation of a single chromosome during meiosis has severe consequences, resulting in defective or inviable progeny. Probing the underlying molecular mechanisms of meiotic chromosome segregation is essential to understanding how chromosomes disjoin with fidelity and how this process can be perturbed. The sequence of meiotic events in the yeast, Sacchromyces cerevisiae, is fundamentally similar to the analogous events in higher eukaryotes; therefore, yeast serves as an excellent model system for the study of meiotic chromosome segregation. Genetic analysis of meiosis in yeast has provided a wealth of information concerning how chromosome synapsis and genetic recombination mediate disjunction at the first meiotic division. However, very few genes have been shown to function in other processes essential for homologous chromosome disjunction. This application proposes to use a genetic approach to identify and characterize genes which function to insure homologous chromosome segregation at the first meiotic division. Several meiotic- lethal, recombination-proficient mutants have been isolated. The phenotypes of these mutants, designated mes (meiotic segregation) mutants, suggest that they carry mutations in genes which function to mediate chromosome disjunction without affecting recombination. The mes mutants will be further characterized genetically to determine at what step chromosome segregation has been perturbed. The wild-type genes will be cloned and sequenced. Cytological studies will be performed to localize the MES gene products to specific meiotic structures. Additionally, interacting gene products will be identified using genetic and biochemical approaches. Analysis of function of MES and interacting gene products will provide information about how chromosomes segregate with fidelity during the meiotic cell cycle.
