Decisions, Decisions: DNA Damage Induced Modification of P53 and the Effect of Modifications on P53 Differential Binding to the Dna

Savannah Gabrielle Keating, University of South Carolina

Abstract

p53 is the most frequently mutated tumor suppressor protein in cancer. It is highly regulated, most often via post-translational modifications (PTMs). Different pathways and target genes are differentially activated by p53 and there is much left to understand how this occurs. The regulation of p53 at the post-translational level is incredibly important to its DNA damage response, and, therefore, it is understood that PTMs are often involved in the differential activation of pathways by p53. This project aimed to identify some of the types and locations of post-translational modifications on p53 in response to different modes of DNA damage with the hopes of then examining the impact specific modifications on p53’s ability to bind to specific sites. Multiple modifications in response to different modes of DNA damage were observed, and it appears that at some level these modifications do play a role in p53’s differential DNA binding abilities.