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Mutations in the Trp53 gene of UV-irradiated Xpc mutant mice suggest a novel Xpc-dependent DNA repair process
- Source :
-
DNA Repair . Apr2004, Vol. 3 Issue 4, p379. 8p. - Publication Year :
- 2004
-
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. [Copyright &y& Elsevier]
- Subjects :
- *MUTAGENESIS
*GENES
*TUMORS
*SKIN cancer
*XERODERMA pigmentosum
Subjects
Details
- Language :
- English
- ISSN :
- 15687864
- Volume :
- 3
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- DNA Repair
- Publication Type :
- Academic Journal
- Accession number :
- 12433155
- Full Text :
- https://doi.org/10.1016/j.dnarep.2003.03.001