ACTIVATION OF P53 SEQUENCE-SPECIFIC DNA-BINDING BY SHORT SINGLE STRANDS OF DNA REQUIRES THE P53 C-TERMINUS

Upon cellular DNA damage, the p53 tumor suppressor protein transmits a signal to genes that control the cell cycle and apoptosis. One functi on of p53 that is important for its role in this pathway is its abilit y to function as a sequence-specific transcriptional activator. We dem onstrate here that short single DNA strands can markedly stimulate the ability of human and murine p53 proteins to bind specifically to a p5 3 response element in supercoiled DNA. We also show that single-strand ed DNA does not stimulate binding by a truncated p53 that lacks the C- terminal domain. Finally, we establish that a peptide spanning the p53 C-terminus has the ability in trans to stimulate sequence-specific DN A binding by p53 dramatically. These data taken together suggest a mod el in which the p53 C-terminus can recognize DNA structures resulting from damage-induced lesions, and this interaction can be propagated to regulate positively p53 sequence-specific DNA binding.