Characterization of defective nucleotide excision repair in XPC mutant mice

David L. Cheo, Hendrick J T Ruven, Lisiane B. Meira, Robert E Hammer, Dennis K Burns, Nancy J. Tappe, Albert A. Van Zeeland, Leon H F Mullenders, Errol C Friedberg

Research output: Contribution to journalArticlepeer-review

106 Scopus citations


Nucleotide excision repair (NER) is a fundamental process required for maintaining the integrity of the genome in cells exposed to environmental DNA damage. Humans defective in NER suffer from the hereditary cancer-prone disease xeroderma pigmentosum. In order to model this disease in mice a mutation in the mouse XPC gene was generated and used to replace a wild-type XPC allele in mouse embryonic stem cells by homologous recombination. These cells were used to derive XPC mutant mice. Fibroblasts from mutant embryos were more sensitive to the cytotoxic effects of ultraviolet light than wild-type and heterozygous cells. Repair synthesis of DNA following irradiation with ultraviolet light was reduced in these cells, indicating a defect in NER. Additionally, XPC mutant embryo fibroblasts were specifically defective in the removal of pyrimidine (6-4) pyrimidone photoproducts from the non-transcribed strand of the transcriptionally active p53 gene. Mice defective in the XPC gene appear to be an excellent model for studying the role of NER and its interaction with other proteins in the molecular pathogenesis of cancer in mammals following exposure to environmental carcinogens.

Original languageEnglish (US)
Pages (from-to)1-9
Number of pages9
JournalMutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
Issue number1
StatePublished - Mar 4 1997


  • Nucleotide excision repair
  • XPC mutant mouse
  • Xeroderma pigmentosum

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Health, Toxicology and Mutagenesis


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