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

G T van der Horst; H van Steeg; R J Berg; A J van Gool; J de Wit; G Weeda; H Morreau; R B Beems; C F van Kreijl; F R de Gruijl; D Bootsma; J H Hoeijmakers

doi:10.1016/s0092-8674(00)80223-8

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.

Authors

G T van der Horst¹, H van Steeg, R J Berg, A J van Gool, J de Wit, G Weeda, H Morreau, R B Beems, C F van Kreijl, F R de Gruijl, D Bootsma, J H Hoeijmakers

Affiliation

¹ Medical Genetics Center, Department of Cell Biology and Genetics, Erasmus University Rotterdam, The Netherlands.

PMID: 9150142
DOI: 10.1016/s0092-8674(00)80223-8

Abstract

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

Substances

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