Mutations in the Trp53 gene of UV-irradiated Xpc mutant mice suggest a novel Xpc-dependent DNA repair process
| Autor: | Susana Velasco-Miguel, Errol C. Friedberg, Dorit Nahari, Laurie B. Task, Russell L Daniel, Lisa D. McDaniel |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Xeroderma pigmentosum
DNA Repair Ultraviolet Rays DNA repair Mutant Population Biology Biochemistry Mice chemistry.chemical_compound medicine Animals Codon education Molecular Biology Gene DNA Primers education.field_of_study Base Sequence integumentary system Cell Biology Genes p53 medicine.disease Molecular biology Mice Mutant Strains DNA-Binding Proteins chemistry Mutation Skin cancer DNA Nucleotide excision repair |
| Zdroj: | DNA Repair. 3:379-386 |
| ISSN: | 1568-7864 |
| Popis: | Mutational hot spots in the human p53 gene are well established in tumors in the human population and are frequently negative prognosticators of the clinical outcome. We previously developed a mouse model of skin cancer with mutations in the xeroderma pigmentosum group C gene (Xpc). UVB radiation-induced skin cancer is significantly enhanced in these mice when they also carry a mutation in one copy of the Trp53 gene (Xpc-/-Trp53+/-). Skin tumors in these mice often contain inactivating mutations in the remaining Trp53 allele and we have previously reported a novel mutational hot spot at a non-dipyrimidine site (ACG) in codon 122 of the Trp53 gene in the tumors. Here we show that this mutation is not a hot spot in Xpa or Csa mutant mice. Furthermore, the mutation in codon T122 can be identified in mouse skin DNA from (Xpc-/-Trp53+/-) mice as early as 2 weeks after exposure to UVB radiation, well before histological evidence of dysplastic or neoplastic changes. Since this mutational hot spot is not at a dipyrimidine site and is apparently Xpc-specific, we suggest that some form of non-dipyrimidine base damage is normally repaired in a manner that is distinct from conventional nucleotide excision repair, but that requires XPC protein. |
| Databáze: | OpenAIRE |
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