Meiosis is process by which eukaryotic organisms, including yeast and humans, produce gametes for sexual reproduction. During meiosis, chromosomes of diploid cells undergo replication followed by two successive segregation events to produce haploid gametes. Homologous chromosomes must pair and recombine to segregate properly at the first division. Homolog pairing is a universal feature of meiosis. Strategies for homolog pairing are conserved among organisms; however, one mechanism may dominate from one organism to the next. Homolog pairing in budding yeast is primarily mediated by double-strand break initiated recombination. Prior to this work, few studies examined the contribution of recombination-independent events in budding yeast. In this study, the contribution of double-strand break repair factors, axial element components, actin-mediated movement were analyzed using a site-specific recombination assay that measures the relative spatial proximity of pairs of chromosomal loci. This assay monitors interactions between identical positions on homologous chromosomes (allelic) and with nonhomologous chromosomes (ectopic). Here analysis of mutants defective in carrying out various stages of recombination points to the strand invasion step of double-strand break repair as being critically important for establishing close stable homolog juxtaposition. Moreover, an unexpected role for chromosome movement was uncovered. While there is a long-standing consensus in the field that the bouquet arrangement facilitates homolog pairing, we found that the bouquet also promotes interactions between ectopic chromosomal loci. Ectopic recombination between nonhomologous chromosomes could have deleterious effects on the chromosome composition of gametes. Our findings suggest that chromosome movement is one mechanism that disrupts the juxtaposition of ectopic chromosomal loci. A second way to prevent nonspecific chromosome interactions requires the meiosis-specific cohesin component Rec8. That is modification of chromosome structure prevents nonspecific associations. Error in chromosome transmission during the formation of gametes is the largest contributing factor of birth defects in humans. Understanding of the biology underlying these errors may contribute to advances that will limit these outcomes in the future.
|Advisor:||Burgess, Sean M.|
|Commitee:||Engebrecht, JoAnne, Hunter, Neil|
|School:||University of California, Davis|
|Department:||Biochemistry and Molecular Biology|
|School Location:||United States -- California|
|Source:||DAI-B 71/06, Dissertation Abstracts International|
|Keywords:||Bouquet, Budding yeast, Homolog pairing, Meiosis, Recombination|
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