p53 is commonly referred to as the "guardian of the genome". Data from multiple experimental models demonstrate a critical and direct role for the p53 family of proteins in protecting organisms from the effects of genetic mutations.

When cells or organisms experience genotoxic or other forms of damage, p53 is activated and binds to a conserved DNA sequence and activates transcription of cell and organism-protective genes. We will use genomic and systems concepts to uncover how p53 properly activates its target genes in reponse to various cellular insults.