Defective transcription-coupled repair in Cockayne syndrome B mice is associated with skin cancer predisposition

Cell. 1997 May 2;89(3):425-35. doi: 10.1016/s0092-8674(00)80223-8.


A mouse model for the nucleotide excision repair disorder Cockayne syndrome (CS) was generated by mimicking a truncation in the CSB(ERCC6) gene of a CS-B patient. CSB-deficient mice exhibit all of the CS repair characteristics: ultraviolet (UV) sensitivity, inactivation of transcription-coupled repair, unaffected global genome repair, and inability to resume RNA synthesis after UV exposure. Other CS features thought to involve the functioning of basal transcription/repair factor TFIIH, such as growth failure and neurologic dysfunction, are present in mild form. In contrast to the human syndrome, CSB-deficient mice show increased susceptibility to skin cancer. Our results demonstrate that transcription-coupled repair of UV-induced cyclobutane pyrimidine dimers contributes to the prevention of carcinogenesis in mice. Further, they suggest that the lack of cancer predisposition in CS patients is attributable to a global genome repair process that in humans is more effective than in rodents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Amino Acid Sequence
  • Animals
  • Cockayne Syndrome / genetics*
  • Cockayne Syndrome / physiopathology
  • DNA Helicases / deficiency
  • DNA Helicases / genetics
  • DNA Repair / physiology*
  • DNA Repair / radiation effects
  • DNA Repair Enzymes
  • Disease Models, Animal
  • Female
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Mutagenesis / physiology
  • Photosensitivity Disorders / genetics
  • Photosensitivity Disorders / physiopathology
  • Poly-ADP-Ribose Binding Proteins
  • Repressor Proteins / genetics
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / physiopathology
  • Transcription Factors / genetics
  • Transcription, Genetic / physiology*
  • Transcription, Genetic / radiation effects
  • Ultraviolet Rays / adverse effects
  • Viral Proteins / genetics
  • Viral Regulatory and Accessory Proteins


  • Poly-ADP-Ribose Binding Proteins
  • Repressor Proteins
  • Transcription Factors
  • Viral Proteins
  • Viral Regulatory and Accessory Proteins
  • phage repressor proteins
  • DNA Helicases
  • ERCC6 protein, human
  • Ercc6 protein, mouse
  • DNA Repair Enzymes