Research in our group is focused on two transcription factors that respond to DNA damage and play important roles in regulating tumor development: E2F1 and p53.
The Johnson lab, located near Austin at Science Park, is keenly interested in the proteins E2F1 and p53. E2F1 and p53 are both transcription factors that respond to DNA damage and regulate tumor formation.
E2F1 is a regulator of genes important for cell cycle progression and apoptosis. We have discovered that E2F1 localizes to sites of both DNA double-strand breaks and UV-induced DNA damage and that this involves the phosphorylation of E2F1 by the ATM or ATR kinases. We have also found that E2F1 recruits chromatin-modifying enzymes to sites of damge to help the DNA repair machinery gain access to DNA. We are now working toward understanding the physiological relevance of E2F1 in the DNA damage response using our new knock-in mouse model that blocks E2F1 phosphorylation by ATM/ATR.
p53 acts as a tumor suppressor helping to prevent cancer formation. We are also exploring the effect of a single nucleotide polymorphism (SNP) within the human p53 gene that creates either an arginine or a proline at amino acid 72 of the p53 protein. This SNP influences the apoptotic activity of p53 by an unknown mechanism. We are exploring the similarities and differences between the apoptotic and other activities of the variant proteins encoded by these two SNPs using knock-in mouse models.