| First Author | Nahari D | Year | 2004 |
| Journal | DNA Repair (Amst) | Volume | 3 |
| Issue | 4 | Pages | 379-86 |
| PubMed ID | 15010313 | Mgi Jnum | J:88558 |
| Mgi Id | MGI:3034118 | Doi | 10.1016/j.dnarep.2003.03.001 |
| Citation | Nahari D, et al. (2004) Mutations in the Trp53 gene of UV-irradiated Xpc mutant mice suggest a novel Xpc-dependent DNA repair process. DNA Repair (Amst) 3(4):379-86 |
| abstractText | 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. |
