Poly(ADP-ribose) binds to specific domains of p53 and alters its DNA binding functions

J Biol Chem. 1998 May 8;273(19):11839-43. doi: 10.1074/jbc.273.19.11839.

Abstract

DNA strand breaks are potential interaction sites for the nuclear enzyme poly(ADP-ribose) polymerase (PARP; E.C. 2.4.2.30) and the tumor suppressor protein p53. Both proteins bind and respond to DNA breaks and both play a role in DNA damage signaling. A temporary colocalization and complex formation between these proteins has been demonstrated in mammalian cells. Here we show that free and poly(ADP-ribose) polymerase-bound ADP-ribose polymers target three domains in p53 protein for strong noncovalent interactions. The polymer binding sites could be mapped to two amino acid sequences in the sequence-specific core DNA binding domain of p53 (amino acid positions 153-178 and 231-253) and another one in the oligomerization domain (amino acids 326-348). In mobility shift experiments, poly(ADP-ribose) effectively prevented and reversed p53 binding to the palindromic p53 consensus sequence. Additionally, poly(ADP-ribose) also interfered with the DNA single strand end binding of p53. The results suggest that ADP-ribose polymers could play a role in regulating the DNA binding properties of p53.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding Sites
  • Binding, Competitive
  • Consensus Sequence
  • DNA, Single-Stranded / metabolism
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Mice
  • Poly (ADP-Ribose) Polymerase-1
  • Poly Adenosine Diphosphate Ribose / metabolism*
  • Poly(ADP-ribose) Polymerases
  • Protein Binding
  • Proteins / metabolism
  • Structure-Activity Relationship
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Proteins
  • Tumor Suppressor Protein p53
  • Poly Adenosine Diphosphate Ribose
  • PARP1 protein, human
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases