Activation of p53 sequence-specific DNA bindingby short single strands of DNA requires the p53 C-terminus

• Published in: Cell Vol. 81; no. 7; pp. 1021 - 1029
• Main Authors: Jayaraman, Lata, Prives, Carol
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 30.06.1995
• ISSN: 0092-8674; 1097-4172
• DOI: 10.1016/S0092-8674(05)80007-8

Upon cellular DNA damage, the p53 tumor suppressor protein transmits a signal to genes that control the cell cycle and apoptosis. One function of p53 that is important for its role in this pathway is its ability to function as a sequence-specific transcriptional activator. We demonstrate here that short single DNA strands can markedly stimulate the ability of human and murine p53 proteins to bind specifically to a p53 response element in supercoiled DNA. We also show that single-stranded 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 DNA binding by p53 dramatically. These data taken together suggest a model 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.