Cockayne syndrome A and B proteins differentially regulate recruitment of chromatin remodeling and repair factors to stalled RNA polymerase II in vivo

Mol Cell. 2006 Aug;23(4):471-82. doi: 10.1016/j.molcel.2006.06.029.

Abstract

Restoration of UV-inhibited transcription requires removal of transcription-blocking DNA lesions by transcription-coupled repair (TCR). In mammals, TCR is dependent on CSA and CSB proteins; however, their functions are largely unknown. Here, we analyzed the composition of UV-stalled transcription elongation complexes from human cells. We show that CSB and CSA display differential roles in recruitment of TCR-specific factors and that assembly for TCR occurs without disruption of the UV-stalled RNA polymerase II (RNAPIIo). CSB fulfills a key role as a coupling factor to attract histone acetyltransferase p300, nucleotide excision repair (NER) proteins, and CSA-DDB1 E3-ubiquitin ligase complex with the COP9 signalosome. CSA is dispensable for attraction of NER proteins to lesion-stalled RNAPIIo, yet in cooperation with CSB is required to recruit XAB2, the nucleosomal binding protein HMGN1, and TFIIS. These results give insight into the nature and order of molecular events that take place during TCR in the context of chromosomal DNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cells, Cultured
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • Cross-Linking Reagents
  • DNA / radiation effects
  • DNA Damage
  • DNA Helicases / metabolism*
  • DNA Repair Enzymes / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism
  • Fibroblasts / radiation effects
  • Humans
  • Models, Genetic
  • Poly-ADP-Ribose Binding Proteins
  • RNA Polymerase II / metabolism*
  • Transcription Factors / metabolism*
  • Transcription, Genetic / radiation effects
  • Transcriptional Elongation Factors / metabolism
  • Ubiquitin-Protein Ligases / metabolism
  • Ultraviolet Rays

Substances

  • Chromosomal Proteins, Non-Histone
  • Cross-Linking Reagents
  • DDB1 protein, human
  • DNA-Binding Proteins
  • ERCC8 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • Transcriptional Elongation Factors
  • XAB2 protein, human
  • transcription factor S-II
  • DNA
  • Ubiquitin-Protein Ligases
  • RNA Polymerase II
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes