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 use genomic and systems concepts to uncover how p53 activates its target genes in reponse to various cellular insults and how cell type, chromatin state, and other factors alter this behavior.
Publications
Determinants of p53 DNA binding, gene regulation, and cell fate decisions
Fischer M and Sammons MA. Cell Death & Differentiation 2024
Context dependent activity of p63-bound gene regulatory elements
McCann AA, et al. bioRxiv 2024
p63 and p53 - collaborative partners or dueling rivals?
Woodstock, et al. Front. Cell Dev. Biol 2021
Tumor suppressor p53 - from engaging DNA to target gene regulation
Sammons MA, et al. Nucleic Acids Research 2020
Control of p53-dependent transcription and enhancer activity by the p53 family member p63
Karsli Uzunbas G, et al. Journal of Biological Chemistry 2019
Comparison of genotoxic vs. non-genotoxic stabilization of p53 provides insight into parallel stress-responsive transcriptional networks
Catizone AN, et al. Cell Cycle 2019
Lysine methylation represses p53 activity in teratocarcinoma cancer cells.
Zhu J et al. PNAS 2016
A rare DNA contact mutation in cancer confers p53 gain-of-function and tumor cell survival via TNFAIP8 induction.
Monteith JA et al. Molecular Oncology 2016
A chromatin-focused siRNA screen for regulators of p53-dependent transcription
Sammons MA et al. G3 2016
Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth
Zhu J et al. Nature 2015
TP53 engagement with the genome occurs in distinct local chromatin environments via pioneer factor activity
Sammons et al. Genome Res 2015