Defective nucleotide excision repair in Xpc mutant mice and its association with cancer predisposition

Errol C. Friedberg, Jeffrey P. Bond, Dennis K. Burns, David L. Cheo, Marc S. Greenblatt, Lisiane B. Meira, Dorit Nahari, Antonio M. Reis

Research output: Contribution to journalArticle

74 Scopus citations

Abstract

Mice that are genetically engineered are becoming increasingly more powerful tools for understanding the molecular pathology of many human hereditary diseases, especially those that confer an increased predisposition to cancer. We have generated mouse strains defective in the Xpc gene, which is required for nucleotide excision repair (NER) of DNA. Homozygous mutant mice are highly prone to skin cancer following exposure to UVB radiation, and to liver and lung cancer following exposure to the chemical carcinogen acetylaminofluorene (AAF). Skin cancer predisposition is significantly augmented when mice are additionally defective in Trp53 (p53) gene function. We also present the results of studies with mice that are heterozygous mutant in the Apex (Hap1, Ref-1) gene required for base excision repair and with mice that are defective in the mismatch repair gene Msh2. Double and triple mutant mice mutated in multiple DNA repair genes have revealed several interesting overlapping roles of DNA repair pathways in the prevention of mutation and cancer. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)99-108
Number of pages10
JournalMutation Research - DNA Repair
Volume459
Issue number2
DOIs
StatePublished - Mar 20 2000

Keywords

  • DNA repair
  • Mismatch repair
  • Msh2 gene
  • Nucleotide excision repair
  • Xeroderma pigmentosum
  • Xpc gene

ASJC Scopus subject areas

  • Molecular Biology
  • Toxicology
  • Genetics

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