The Characterization of Genes Involved in Response to the Phenol Derivative and Xenoestrogen Bisphenol-A in Saccharomyces Cerevisiae
Date of Submission
Open Access Senior Thesis
Bachelor of Arts
W.M. Keck Science Department
© 2011 Sasha Farina
Bisphenol A is an estrogenic compound that is found in polycarbonate plastics and epoxy resins; humans are continuously exposed to the compound and it is believed to possess the same carcinogenic effects as estrogen (Iso, 2006). In this study, I used Saccharomyces cerevisiae as a model organism to identify mechanisms by which BPA acts based on the genomic profiling of kinase genes from a Mat-α haploid deletion library. Kinases regulate many other proteins, so the identification of a single mutant could identify an entire affected pathway of genes. I conducted a systematic screen of these mutants using the phenotype of growth inhibition. Using solid growth assays, I identified 17 BPA sensitive mutants, six of which were related to the high osmolarity growth pathway, which is involved in osmotic stress response and could be a mechanism of defense of S. cerevisiae against BPA. I implemented liquid growth assays, protein analysis, as well as microscopy for a more in depth study of the effects of BPA on these mutants. Bisphenol-A initially inhibits the growth of S. cerevisiae, however, there were some strains that appeared to show adaptation in the presence of the compound. I found that BPA inhibits cell cycle progression, and may affect the phosphorylation regulation of Cdc28, but without affecting the production of the protein. This study provides clues for predicting the effects of BPA on homologous genes in mammals and identifying similar pathways of resistance. By having a better understanding of the effects on BPA on the cell, the compound can be better regulated by the EPA and complications resulting from continuous exposure to BPA can be treated effectively.
Farina, Sasha N., "The Characterization of Genes Involved in Response to the Phenol Derivative and Xenoestrogen Bisphenol-A in Saccharomyces Cerevisiae" (2011). CMC Senior Theses. 221.