CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway establishes a link between complementation factors of the Cockayne syndrome

Genes Dev. 2006 Jun 1;20(11):1429-34. doi: 10.1101/gad.378206.

Abstract

Mutations in the CSA or CSB complementation genes cause the Cockayne syndrome, a severe genetic disorder that results in patients' death in early adulthood. CSA and CSB act in a transcription-coupled repair (TCR) pathway, but their functional relationship is not understood. We have previously shown that CSA is a subunit of an E3 ubiquitin ligase complex. Here we demonstrate that CSB is a substrate of this ligase: Following UV irradiation, CSB is degraded at a late stage of the repair process in a proteasome- and CSA-dependent manner. Moreover, we demonstrate the importance of CSB degradation for post-TCR recovery of transcription and for the Cockayne syndrome. Our results unravel for the first time the functional relationship between CSA and CSB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cockayne Syndrome / genetics*
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • DNA Repair Enzymes / genetics
  • DNA Repair Enzymes / metabolism*
  • Genetic Complementation Test*
  • HeLa Cells
  • Humans
  • Poly-ADP-Ribose Binding Proteins
  • Proteasome Endopeptidase Complex / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Ubiquitin / metabolism*

Substances

  • ERCC8 protein, human
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • Ubiquitin
  • Proteasome Endopeptidase Complex
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes