Transcriptional activators stimulate DNA repair

Mol Cell. 2002 Dec;10(6):1391-401. doi: 10.1016/s1097-2765(02)00732-3.

Abstract

To counteract the deleterious effects of genotoxic injury, cells have set up a sophisticated network of DNA repair pathways. We show that Gal4-VP16 and RAR transcriptional activators stimulate nucleotide excision repair (NER). This DNA repair activation is not coupled to transcription since it occurs in Cockayne syndrome cells (which are transcription-coupled repair deficient) and is observed in vitro in the presence of alpha-amanitin and in the absence of the basal transcription factors. Using a reconstituted dual incision assay, we also show that binding of activators to their cognate sequences induces a local chromatin remodeling mediated by ATP-driven chromatin remodeling and acetyltransferase activities to facilitate DNA repair.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Cell Line, Transformed
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Repair / physiology*
  • DNA-Binding Proteins
  • Herpes Simplex Virus Protein Vmw65 / metabolism
  • Humans
  • Oligodeoxyribonucleotides / chemistry
  • Receptors, Retinoic Acid / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Restriction Mapping
  • Saccharomyces cerevisiae Proteins / metabolism
  • Simian virus 40 / genetics
  • Templates, Genetic
  • Trans-Activators / metabolism*
  • Transcription Factors / metabolism
  • Transcription, Genetic*
  • Transfection

Substances

  • DNA-Binding Proteins
  • GAL4 protein, S cerevisiae
  • Herpes Simplex Virus Protein Vmw65
  • Oligodeoxyribonucleotides
  • Receptors, Retinoic Acid
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Trans-Activators
  • Transcription Factors
  • DNA