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Show HONORS COLLEGE SPRING 2013 Zachary Lee KentGolic 216 USING DROSOPHILA TO INVESTIGATE P53-MEDIATED LIFE-OR-DEATH DECISIONS Zachary Lee (Kent Golic) Department of Biology University of Utah The p53 tumor suppressor is a central regulator of cellular responses to D N A damage. When DNA damage cannot be repaired most cells undergo p53-dependent cell death. This p53-mediated apoptosis is important to eliminate cells with damaged genomes and provides an important block to the development of cancer. However, a minority of cells do survive with D N A damage, and w e wish to understand how this occurs. p53 is a transcriptional regulator with hundreds of identified target genes. W e are exploring the role of p53-regulated genes in determining the fate of such cells. Our experimental method alters the expression levels of p53-regulated genes using transgenic constructs, while simultaneously inducing a non-repairable D N A double-strand break. These effects are limited to the fly eye. Adult flies are examined, with increased eye size indicating enhanced cell survival, and decreased eye size indicating enhanced cell death. Although p53 is primarily known for its role in promoting apoptosis, w e have found that some p53-regulated genes have the opposite effect. W e propose that the ultimate cellular outcome reflects the result of a competition between p53-regulated pro-apoptotic and anti-apoptotic genes. |
