抄録
A C-terminal 183 amino acid-truncated mutation of the mouse Xpg gene (XpgΔex15) gives rise to a partial deficiency in nucleotide excision repair in homozygously affected cells. We studied the effect of this mutation on UVB-induced mutagenesis in mouse skin, using transgenic mice harboring λ-phage-based bacterial lacZ genes as a mutational reporter. UVB increased the lacZ mutant frequency in the epidermis moderately in the homozygous mutant mice, but significantly higher than in the wild-type or the heterozygous mice, whereas background mutant frequencies were not appreciably different among the three mouse genotypes. Ninety-eight lacZ mutant sequences isolated from the UVB-exposed epidermis of the XpgΔex15-homozygous mice were analyzed and compared with mutant sequences from the wild-type mice. The spectra of the mutations in the two mouse genotypes were not significantly different, and they were highly UV-specific. There were frequent C → T transitions at dipyrimidine sites and several CC → TT tandem mutations, although the UV-specific mutations occurred more frequently at CpG sites in the mutant mice. The distribution of the mutations observed in the lacZ transgene and the preferred sequence context of the UV-specific C → T mutations (5′-TC-3′ > 5′-CC-3′ > 5′-CT-3′) in the Xpg-mutant mice were similar to those found in the wild-type mice. Despite these similarities, we detected a previously unrecognized type of the UV-induced mutation only in the Xpg mutant (6/98 in the mutation spectrum of the mutant vs. 0/76 in the wild-type; P = 0.035), which is characterized by multiple base substitutions or frameshifts within a three-nucleotide sequence containing a dipyrimidine. We propose that this putative new class of mutation, which we refer to as a "triplet mutation", is characteristic of UV-induced mutation in an excision-repair-deficient background.
本文言語 | English |
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ページ(範囲) | 107-116 |
ページ数 | 10 |
ジャーナル | Environmental and Molecular Mutagenesis |
巻 | 47 |
号 | 2 |
DOI | |
出版ステータス | Published - 2006 3月 |
ASJC Scopus subject areas
- 疫学
- 遺伝学(臨床)
- 健康、毒物学および変異誘発