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

• Published in: Mutation Research-DNA Repair Vol. 459; no. 2; pp. 99 - 108
• Main Authors: Friedberg, Errol C., Bond, Jeffrey P., Burns, Dennis K., Cheo, David L., Greenblatt, Marc S., Meira, Lisiane B., Nahari, Dorit, Reis, Antonio M.
• Format: Book Review Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 20.03.2000; Elsevier
• Subjects: acetylaminofluorene; Animals; Biological and medical sciences; Carbon-Oxygen Lyases - genetics; DNA Repair; DNA-(Apurinic or Apyrimidinic Site) Lyase; DNA-Binding Proteins - genetics; DNA-Binding Proteins - physiology; Fundamental and applied biological sciences. Psychology; Genetic Predisposition to Disease; Humans; Liver Neoplasms - genetics; Lung Neoplasms - genetics; Mice; Mice, Knockout; Mismatch repair; Molecular and cellular biology; Molecular genetics; Msh2 gene; Mutagenesis. Repair; MutS Homolog 2 Protein; Neoplasms - genetics; Nucleotide excision repair; p53 gene; Proto-Oncogene Proteins - genetics; Skin Neoplasms - genetics; Trp53 gene; Tumor Suppressor Protein p53 - genetics; Xeroderma pigmentosum; Xeroderma Pigmentosum - genetics; Xpc gene; Xeroderma pigmentosum; Nucleotide excision repair; DNA repair; Mismatch repair; Xpc gene; Msh2 gene; Photosensitivity; Skin disease; Pigmentation disorder; Excision; p53 Protein; Rodentia; Genetic disease; Carcinogen; Photodermatosis; Vertebrata; Mammalia; Gene; Ultraviolet irradiation; Mouse; DNA; Nucleotide; Genetics; Tumor; Lesion; Mutation; Repair; Fluorene derivatives
• ISSN: 0921-8777; 0027-5107; 1386-1476
• DOI: 10.1016/S0921-8777(99)00068-3

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.