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 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.
Jayaraman
J
J
Department of Biological Sciences, Columbia University, New York, New York 10027, USA.
Prives
C
C
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D016384:Consensus Sequence; D017931:DNA Primers; D004277:DNA, Single-Stranded / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D004278:DNA, Superhelical / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism*; D003850:Deoxyribonuclease I; D016158:Genes, p53; D006801:Humans; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D017384:Sequence Deletion; D018411:Spodoptera; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000378:metabolism*
D017931:DNA Primers; D004277:DNA, Single-Stranded; D004278:DNA, Superhelical; D009838:Oligodeoxyribonucleotides; D011994:Recombinant Proteins; D016159:Tumor Suppressor Protein p53; D003850:Deoxyribonuclease I