Mutations in the Trp53 gene of UV-irradiated Xpc mutant mice suggest a novel Xpc-dependent DNA repair process

Dorit Nahari, Lisa D. McDaniel, Laurie B. Task, Russell L. Daniel, Susana Velasco-Miguel, Errol C. Friedberg

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)379-386
Number of pages8
JournalDNA repair
Volume3
Issue number4
DOIs
StatePublished - Apr 1 2004

Keywords

  • Mutation detection
  • Mutational hot spots
  • NER
  • Xpc mice
  • p53 gene

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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