Project Details
Description
9507786 Kaback During meiosis, homologous chromosomes pair, undergo recombination and then segregate from each other. Reciprocal recombination (crossing over) is required for proper pairing and segregation. However, the mechanisms that control recombination and insure that all homologues crossover with each other are not understood. Chromosome I is the smallest Saccharomyces cerevisiae chromosome and contains a DNA molecule that is only 231 kb. This chromosome has been studied extensively and much is known about its meiotic behavior. Recombination rates were mapped over its entire length and were found to be 3-4 fold lower within 20 kb of the centromere and both telomeres. In addition, several recombination 'hot spots' were found to correspond to meiotic double-strand break sites believed to be involved in initiating meiotic recombination. Most important, these studies revealed that small yeast chromosomes had higher reciprocal recombination rates than large yeast chromosomes, an observation that appears to be true in other organisms including humans. High recombination rates were found over most of the physical length of these small chromosomes and appear to be necessary to insure that small chromosomes crossover during meiosis. The investigator discovered that high rates of recombination on small chromosomes were due to a global control mechanism that regulated recombination rates by responding directly to chromosome size. This mechanism was investigated and found to be closely linked to chiasma (crossover) interference. Indeed, the level of chiasma interference was proportional to a function of the chromosome size. Chiasma interference is believed to regulate reciprocal recombination by inhibiting further crossing over in regions that have already recombined. Its mechanism is unknown but may involve the synaptonemal complex. To better understand the mechanisms that control recombination and insure that all chromosomes crossover with their homologues, the investigator will study how chias ma interference responds directly to chromosome size. He has proposed a model for this control and experiments to test the model. The model predicts that, on average, large chromosomes crossover earlier. As a result, more time is available for interference to occur. Accordingly, on average, single crossovers will affect more DNA on larger chromosomes. This prediction will be tested by measuring the average length of interference tracts on well-marked constructs containing small and large copies of chromosome I. Finally, he will continue two studies on cis acting elements that control recombination. A 50 kb functional chromosome I fragment that segregates from its homologue with a high degree of fidelity has been isolated. This minichromosome recombines at very high rates and is believed to contain only a single meiotic double-strand break site. He will investigate this construct and use it to critically test the hypothesis that meiotic double-strand break sites are required for proper meiotic pairing and recombination. He will also complete studies that appear to show that telomeres inhibit recombination in subtelomeric regions. The zone of telomeric inhibition will be measured. He will also determine if the SIR3 gene, which is involved in telomeric repression of gene expression, is also involved in suppressing meiotic recombination. In total, these studies will further our understanding of how recombination is controlled so that homologous chromosomes pair and segregate properly during meiosis. %%% For sexual reproduction, cells which have two copies of each chromosome (diploid cells) must give rise to cells which have only one copy of each chromosome (haploid cells). This process is called meiosis. During meiosis a diploid nucleus normally undergoes replication and then two divisions, meiosis I and meiosis II, producing four haploid nuclei. At meiosis I homologous chromosomes pair and exchange genetic material (recombine). Reciprocal recombination between homologues is believed to be essential for proper pairing and segregation of chromosomes. The mechanisms that control meiotic recombination so each chromosome recombines with its homologue are not fully understood. The scientist will investigate these mechanisms. ***
Status | Finished |
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Effective start/end date | 7/15/95 → 6/30/98 |
Funding
- National Science Foundation: $360,000.00