title: Strand specificity and absence of hot spots for p53 mutations in ultraviolet B-induced skin tumors of XPA-deficient mice.
abstract: We examined the spectrum of p53 mutations found in 40 UV-induced skin tumors of xeroderma pigmentosum group A gene (XPA)-deficient mice. p53 mutations were detected in 48% of the tumors. Nearly all of the mutations were induced at dipyrimidine sites. Ninety-three % of the mutations were G.C-->A.T transitions at dipyrimidine sites, including tandem transitions (CC-->TT), which are the hallmark of the UVB-induced mutation. Seventy-two % of the mutations at dipyrimidine sites could be ascribed to damage on the transcribed strand. In addition, no evident mutational hot spots were detected. This is in contrast to the UVB-induced skin tumors of normal mice, in which 92% of p53 mutations occurred as a result of DNA damage on the nontranscribed strand, and clear hot spots were observed. Thus, XPA-deficient mice showed significant mutation features that might be characteristic of the absence of nucleotide excision repair and may provide a good animal model for the analysis of the high incidence of skin cancer in xeroderma pigmentosum group A patients.
authors.affiliation: Division of Cellular Genetics, Institute for Molecular and Cellular Biology, Osaka University, Suita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takeuchi
authors.forename: Y
authors.initials: Y
authors.lastname: Nakatsu
authors.forename: H
authors.initials: H
authors.lastname: Nakane
authors.forename: H
authors.initials: H
authors.lastname: Murai
authors.forename: S
authors.initials: S
authors.lastname: Hirota
authors.forename: Y
authors.initials: Y
authors.lastname: Kitamura
authors.forename: A
authors.initials: A
authors.lastname: Okuyama
authors.forename: K
authors.initials: K
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D001483:Base Sequence; D016158:Genes, p53; D006801:Humans; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D009381:Neoplasms, Radiation-Induced / Q000235:genetics*; D012878:Skin Neoplasms / Q000235:genetics*; D014466:Ultraviolet Rays; D014983:Xeroderma Pigmentosum / Q000235:genetics*