| Description |
The p53 tumor suppressor is a central regulator of cellular responses to DNA damage. When DNA damage cannot be repaired most cells undergo p53-dependent cell death. Thisp55-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 DNA damage, and we wish to understand how this occurs. p53 is a transcriptional regulator with hundreds of identified target genes. We are exploring the role of p53-regulated genes in determining the fate of such cells. Our experimental method alters the expression levels of/>53-regulated genes using transgenic constructs, while simultaneously inducing a non-repairable DNA 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. Althoughp53 is primarily known for its role in promoting apoptosis, we have found that somep53-regulated genes have the opposite effect. We propose that the ultimate cellular outcome reflects the result of a competition between p53-regulated pro-apoptotic and anti-apoptotic genes. |
