title: Mutations in the Trp53 gene of UV-irradiated Xpc mutant mice suggest a novel Xpc-dependent DNA repair process.
abstract: 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.
authors.affiliation: Laboratory of Molecular Pathology, Department of Pathology, University of Texas, Southwestern Medical Center, Dallas, TX 75390-9072, USA.
authors.forename: Dorit
authors.initials: D
authors.lastname: Nahari
authors.forename: Lisa D
authors.initials: LD
authors.lastname: McDaniel
authors.forename: Laurie B
authors.initials: LB
authors.lastname: Task
authors.forename: Russell L
authors.initials: RL
authors.lastname: Daniel
authors.forename: Susana
authors.initials: S
authors.lastname: Velasco-Miguel
authors.forename: Errol C
authors.initials: EC
authors.lastname: Friedberg
mesh_terms: D000818:Animals; D001483:Base Sequence; D003062:Codon; D017931:DNA Primers; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016158:Genes, p53; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D014466:Ultraviolet Rays
chemical_list: D003062:Codon; D017931:DNA Primers; D004268:DNA-Binding Proteins; C501002:Xpc protein, mouse