Date of Award

Fall 2019

Document Type

Open Access Thesis

Department

Biological Sciences

First Advisor

David Reisman

Abstract

p53 is a powerful tumor suppressor mutated in approximately half of all cancers. Its mRNA is stabilized post-transcriptionally via complementary base pairing with the transcript of its antisense gene, WRAP53α; without this interaction, p53 protein cannot accumulate enough to carry out its many functions related to apoptosis, cell cycle arrest, and DNA damage repair. Previous studies have shown that WRAP53α is induced in response to DNA damage. The purpose of this study was to determine which transcription factors might be responsible for this induction. After identifying three putative p53 binding sites on the WRAP53α promoter, we used chromatin immunoprecipitation and site-directed mutagenesis and found that p53 appears to bind several sites on the WRAP53α promoter in a manner dependent upon the type of DNA damage. Similarly, we found that deletion of these sites leads to a loss in induction. Although more experimentation is needed, these findings indicate a regulatory positive feedback loop between WRAP53α and p53, which may be important in mounting a proper DNA damage response. This positive feedback loop may be used in targeted cancer therapy.

Rights

© 2019, Anne Shelton Hucks

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