Molecular Organization of Yeast Chromosome I - Control of Meiotic Pairing and Recombination

Project Details

Description

SUMMARY

Reciprocal recombination (crossing over) between homologous chromosomes (homologues) appears to be required for proper meiosis I segregation. The mechanisms that control recombination so that each pair of homologues undergoes crossing over are not known. In Saccharomyces cerevisiae and humans, small chromosomes have higher meiotic reciprocal recombination rates (cM/kb) than large chromosomes and in S. cerevisiae rates of reciprocal recombination have been shown to respond directly to chromosome size. The increased rates of recombination on small chromosomes appear to ensure crossing over and have been proposed to be due to crossover interference. Interference is defined by the apparent inhibition of additional meiotic reciprocal recombination events observed near the site of a crossover. The molecular mechanism of interference and how it might respond to chromosome size are not known. It was recently suggested that the density of meiotic recombination-inducing double-strand break (DSB) sites is greater on small chromosomes compared to large chromosomes suggesting chromosome size dependent control of recombination and perhaps interference might act by controlling DSB formation. To test this idea, we propose to analyze DSB formation on different size chromosome I constructs that were constructed in our laboratory. It has also been suggested that the meiotic synaptonemal complex (SC) is involved in mediating interference. Accordingly, a better understanding of the mechanism of interference might be gained by investigating the S. cerevisiae SC. Using a functional, fluorescent ZIP1-GFP fusion protein constructed in our laboratory, we have shown that SCs undergo dynamic changes in their distribution in early and late pachytene. We now propose to examine the dynamics of SC movements using ZIP1-GFP in mutant yeast in order to determine the genes required to produce this reorganization. We also propose to address the relationship of this reorganization to crossover interference. The structure and dynamics of the fluorescent SC will be examined using optical sections and fluorescent cinema-microscopy and will be enhanced by the construction of additional ZIP1-fluorocent protein fusions. These studies should provide new insight into the molecular mechanisms controlling recombination and chromosome synapsis, processes that lead to proper meiotic chromosome segregation.

StatusFinished
Effective start/end date6/1/0212/31/05

Funding

  • National Science Foundation: $475,000.00

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