Mutation spectrum in UVB‐exposed skin epidermis of a mildly‐affected Xpg‐deficient mouse
Mutation spectrum in UVB‐exposed skin epidermis of a mildly‐affected Xpg‐deficient mouse
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DOI：
10.1002/em.20173
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发表时间：
2006-03
影响因子：
2.8
通讯作者：
Feng Wang;Yusuke Saito;T. Shiomi;S. Yamada;T. Ono;H. Ikehata
中科院分区：
文献类型：
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作者：
Feng Wang;Yusuke Saito;T. Shiomi;S. Yamada;T. Ono;H. Ikehata
小鼠XPG基因(XPGΔEX15)的C端183个氨基酸截断突变导致纯合子感染细胞中核苷酸切除修复的部分缺陷。我们以携带基于λ噬菌体的细菌LacZ基因的转基因小鼠为突变报告，研究了该突变对中波紫外线诱导小鼠皮肤突变的影响。UVB可适度增加纯合子突变小鼠表皮LacZ突变频率，但显著高于野生型和杂合子小鼠，而背景突变频率在三种小鼠基因型间无显著差异。从紫外线照射的XPGΔEX15纯合子小鼠的表皮中分离到98个LacZ突变序列，并与野生型小鼠的突变序列进行了比较。这两种小鼠基因突变的光谱没有显著差异，而且它们具有高度的紫外线专一性。在突变小鼠中，存在频繁的双嘧啶C→T转换和几个CC→TT串联突变，但UV特异性突变更频繁地发生在CpG位点。在XpG基因突变小鼠中观察到的LacZ转基因突变的分布和UV特异性C→T突变(5‘-TC-3’>；5‘-CC-3’>；5‘-CT-3’)的首选序列背景与在野生型小鼠中发现的相似。尽管有这些相似之处，我们只在Xpg突变体中检测到了一种以前未被识别的紫外线诱导突变类型(突变体的突变谱中为6/98，而野生型中为0/76；P=0.035)，其特征是含有二嘧啶的三核苷酸序列中的多个碱基替换或移码。我们认为这种假定的新类型的突变，我们称之为“三联体突变”，是在切除修复缺陷的背景下紫外线诱导的突变的特征。环境。摩尔。《诱变剂》，2006年。©2005 Wiley-Liss Inc.
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. Environ. Mol. Mutagen., 2006. © 2005 Wiley‐Liss, Inc.