Association of CBP/p300 Acetylase and Thymine DNA Glycosylase Links DNA Repair and Transcription

Mol Cell. 2002 Feb;9(2):265-77. doi: 10.1016/s1097-2765(02)00453-7.

Abstract

DNA repair in chromatin is subject to topological constraints, suggesting a requirement for chromatin modification and remodeling activities. Thymine DNA glycosylase (TDG) initiates repair of G/T and G/U mismatches, commonly associated with CpG islands, by removing thymine and uracil moieties. We report that TDG associates with transcriptional coactivators CBP and p300 and that the resulting complexes are competent for both the excision step of repair and histone acetylation. Furthermore, TDG stimulates CBP transcriptional activity in transfected cells and reciprocally serves as a substrate for CBP/p300 acetylation. Remarkably, this acetylation triggers release of CBP from DNA ternary complexes and also regulates recruitment of repair endonuclease APE. These observations reveal a potential regulatory role for protein acetylation in base mismatch repair and a role for CBP/p300 in maintaining genomic stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Animals
  • Base Pair Mismatch / genetics*
  • COS Cells
  • Cell Transformation, Neoplastic
  • Chlorocebus aethiops
  • Chromatin / genetics
  • Chromatin / ultrastructure
  • CpG Islands
  • DNA Damage
  • DNA Repair / physiology*
  • Deoxyribonuclease (Pyrimidine Dimer)
  • E1A-Associated p300 Protein
  • Endodeoxyribonucleases / chemistry
  • Endodeoxyribonucleases / genetics
  • Endodeoxyribonucleases / physiology*
  • Genes, Tumor Suppressor
  • Histones / metabolism
  • Macromolecular Substances
  • Mice
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • Protein Interaction Mapping
  • Protein Processing, Post-Translational / physiology*
  • Protein Structure, Tertiary
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / physiology
  • Sequence Deletion
  • Trans-Activators / chemistry
  • Trans-Activators / genetics
  • Trans-Activators / physiology*
  • Transcription, Genetic / physiology*
  • Transfection
  • Two-Hybrid System Techniques

Substances

  • Chromatin
  • Histones
  • Macromolecular Substances
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • E1A-Associated p300 Protein
  • Ep300 protein, mouse
  • Endodeoxyribonucleases
  • Deoxyribonuclease (Pyrimidine Dimer)