Meiosis is a specialized cell division that leads to a reduction of ploidy in sexually reproducing organisms through segregation of homologous chromosomes at the first meiotic division. Improper segregation of chromosomes during meiosis results in anueploidy, which is usually fatal during embryonic development. The meiotic process is therefore tightly regulated. Typically, proper segregation of homologs at meiosis I requires pairing of homologous chromosomes, followed by crossover recombination between homologs. Crossovers enable proper chromosomal segregation during the first meiotic division in part by establishing tension in the meiotic spindle. However, in the absence of crossovers, some cells maintain the ability to direct homologous chromosomes to opposite spindle poles, through a poorly understood mechanism known as distributive segregation. We are using the common brewers yeast Saccharomyces cerevisiae to determine possible roles of two genes in distributive segregation. The genes of interest, Ndj1 and Tid1, have been previously demonstrated to play a role in crossover interference, but their roles in distributive segregation are not well understood. Ndj1 has been shown to function in the tethering of telomeres to the nuclear envelope and may aid in the homology search chromosomes undergo. Tid1 has been characterized as a recombination accessory factor and may stimulate crossovers by directing recombinases to double strand break sites early in meiosis. To assay distributive segregation, we use yeast in which crossing over between one chromosome pair is prevented (due to sequence divergence). Using this system, we can assay the ability of yeast to carry out distributive segregation. Our results indicate that mutations in Ndj1 impair the ability of yeast to carry out distributive segregation, while mutations in Tid1 do not affect distributive segregation. These results, in turn, suggest that Ndj1 may play a role in distributive segregation. This experiment is part of a larger question to determine whether crossover assurance and crossover interference are independent mechanisms.

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<p>Endopolyploid cells (hereafter - polyploid cells), which contain whole genome duplications in an otherwise diploid organism, play vital roles in development and physiology of diverse organs such as our heart and liver. Polyploidy is also observed with high frequency in many tumors, and division of such cells frequently creates aneuploidy (chromosomal imbalances), a hallmark of cancer. Despite its frequent occurrence and association with aneuploidy, little is known about the specific role that polyploidy plays in diverse contexts. Using a new model tissue, the Drosophila rectal papilla, we sought to uncover connections between polyploidy and aneuploidy during organ development. Our lab previously discovered that the papillar cells of the Drosophila hindgut undergo developmentally programmed polyploid cell divisions, and that these polyploid cell divisions are highly error-prone. Time-lapse studies of polyploid mitosis revealed that the papillar cells undergo a high percentage of tripolar anaphase, which causes extreme aneuploidy. Despite this massive chromosome imbalance, we found the tripolar daughter cells are viable and support normal organ development and function, suggesting acquiring extra genome sets enables a cell to tolerate the genomic alterations incurred by aneuploidy. We further extended these findings by seeking mechanisms by which the papillar cells tolerated this resultant aneuploidy.</p> / Dissertation

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