Meiosis (the special division process that occurs in the developmental pathway to produce sexual gametes) is a ubiquitous process in eucaryotes. The two unique events that occur only in meiosis are high levels of recombination and pairing between homologous chromosomes, and the subsequent reductional division that reduces the chromosome number from 2N to 1N. Our work is directed at understanding how the first distinctive meiotic event of chromosome recombination and pairing begins in the yeast, Saccharomyces cerevisiae. We have defined, cloned, and partially characterized three new genes (REC102, REC104, and REC114) that are required for the initiation of recombination. (There are now 8 """"""""early"""""""" recombination genes known, plus at least 3 whose role seems to be primarily in chromosome pairing.) We propose to finish the characterization of these 3 genes, as well as examining how the early Rec gene products interact with other components of both the exchange and the pairing pathways. To understand how the initiation of recombination is coordinated, experiments designed to understand the regulation of REC102, REC104, and REC114 are presented; we have already shown that their expression is meiosis specific. Finally, we propose experiments to determine the activity of the REC gene products. Early REC genes are not the only components involved in recombination. Certain regions of chromosomes recombine more frequently than others. We have studied such a region around the HIS2 gene, and have discovered that the DNA sequences required for high level conversion appear to be located 800 bp downstream of the gene. Experiments are proposed to determine exactly what cis acting sequences are necessary; formally, this is analogous to defining what sequences are necessary for replication origins or transcriptional promoters. We have also observed that these sequences may not be sufficient for initiation when moved to other chromosomes, suggesting that other factors may play a role in meiotic recombination initiation. Thus, experiments are proposed to investigate the structure of the chromosome around the HIS2 gene, and to determine how it contributes to recombination. Thus, the two major parts of this proposal each study a different, but related, component required for the initiation of recombination in meiosis. At the chromosome level, meiosis is incredibly conserved: Mendel's laws hold as well for man and baker's yeast as they do for peas; we therefore expect that what we find about yeast will apply to other eucaryotes.
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