Structural basis of ubiquitin recognition by the winged-helix domain of Cockayne syndrome group B protein

Nucleic Acids Res. 2019 Apr 23;47(7):3784-3794. doi: 10.1093/nar/gkz081.


Cockayne syndrome group B (CSB, also known as ERCC6) protein is involved in many DNA repair processes and essential for transcription-coupled repair (TCR). The central region of CSB has the helicase motif, whereas the C-terminal region contains important regulatory elements for repair of UV- and oxidative stress-induced damages and double-strand breaks (DSBs). A previous study suggested that a small part (∼30 residues) within this region was responsible for binding to ubiquitin (Ub). Here, we show that the Ub-binding of CSB requires a larger part of CSB, which was previously identified as a winged-helix domain (WHD) and is involved in the recruitment of CSB to DSBs. We also present the crystal structure of CSB WHD in complex with Ub. CSB WHD folds as a single globular domain, defining a class of Ub-binding domains (UBDs) different from 23 UBD classes identified so far. The second α-helix and C-terminal extremity of CSB WHD interact with Ub. Together with structure-guided mutational analysis, we identified the residues critical for the binding to Ub. CSB mutants defective in the Ub binding reduced repair of UV-induced damage. This study supports the notion that DSB repair and TCR may be associated with the Ub-binding of CSB.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • Cell Survival
  • Cockayne Syndrome / genetics
  • Cockayne Syndrome / metabolism
  • DNA Breaks, Double-Stranded*
  • DNA Damage / genetics
  • DNA Damage / radiation effects
  • DNA Helicases / chemistry*
  • DNA Helicases / genetics
  • DNA Repair / genetics
  • DNA Repair / radiation effects
  • DNA Repair Enzymes / chemistry*
  • DNA Repair Enzymes / genetics
  • Humans
  • Mutation
  • Poly-ADP-Ribose Binding Proteins / chemistry*
  • Poly-ADP-Ribose Binding Proteins / genetics
  • Protein Conformation, alpha-Helical / genetics
  • Ubiquitin / chemistry*
  • Ubiquitin / genetics
  • Ubiquitins / chemistry*
  • Ubiquitins / genetics
  • Ultraviolet Rays
  • Winged-Helix Transcription Factors / chemistry*
  • Winged-Helix Transcription Factors / genetics


  • Poly-ADP-Ribose Binding Proteins
  • Ubiquitin
  • Ubiquitins
  • Winged-Helix Transcription Factors
  • DNA Helicases
  • ERCC6 protein, human
  • DNA Repair Enzymes