Repair of oxidatively damaged guanine in Saccharomyces cerevisiae by an alternative pathway
Repair of oxidatively damaged guanine in Saccharomyces cerevisiae by an alternative pathway
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DOI：
10.1016/s0960-9822(98)70158-7
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发表时间：
1998-03-26
期刊：
影响因子：
9.2
通讯作者：
Verdine, GL
中科院分区：
文献类型：
--
作者：
Bruner, SD;Nash, HM;Verdine, GL
背景资料：颠换突变是由8-氧代鸟嘌呤（（O）G）引起的，这是一种由鸟嘌呤核苷酸自发氧化产生的DNA损伤，在复制过程中与腺嘌呤错配。对这种诱变威胁的抗性由GO系统介导，GO系统的组分在细菌和哺乳动物中功能保守。迄今为止，在芽殖酵母酿酒酵母中仅鉴定出三种GO系统组分中的一种，即（O）G：C特异性糖基化酶/裂解酶yOgg 1。此外，S.据报道，酿酒酵母含有独特的糖基化酶/裂解酶活性yOgg 2，其切除与腺嘌呤相对的（O）G残基。特别是，根据目前公认的模型，yOgg 2活性应增加（O）G病变的致突变性。在这里，我们报告的yOgg 2的分离和阐明其在氧化mutagenetrans.Results的作用：使用（O）G-含有寡核苷酸，基板硼氢化钠依赖性交联导致分离的yOgg 1和第二个蛋白质，Ntg 1，它以前已被证明在DNA中处理氧化嘧啶。结果表明，Ntg 1具有与yOgg 2相同的（O）G特异性糖基化酶/裂解酶活性，NTG 1基因的靶向缺失导致yOgg 2活性完全丧失，缺失NTG 1的酵母具有较高的A：T到C：G的颠换率。我们认为yOgg 2已经进化到处理（O）G：A错配，这些错配是在复制过程中通过错误掺入8-oxo-dGTP而产生的。因此，S.酿酒酵母中的蛋白质与细菌和哺乳动物中的蛋白质根本不同。
Background: Transversion mutations are caused by 8-oxoguanine ((O)G), a DNA lesion produced by the spontaneous oxidation of guanine nucleotides, which mis-pairs with adenine during replication. Resistance to this mutagenic threat is mediated by the GO system, the components of which are functionally conserved in bacteria and mammals. To date, only one of three GO system components has been identified in the budding yeast Saccharomyces cerevisiae, namely the (O)G:C-specific glycosylase/lyase yOgg1. Furthermore, S. cerevisiae has been reported to contain a unique glycosylase/lyase activity, yOgg2, which excises (O)G residues opposite adenines. Paradoxically, according to the currently accepted model, yOgg2 activity should increase the mutagenicity of (O)G lesions. Here we report the isolation of yOgg2 and the elucidation of its role in oxidative mutagenesis.Results: Borohydride-dependent cross-linking using an (O)G-containing oligonucleotide, substrate led to the isolation of yOgg1 and a second protein, Ntg 1, which had previously been shown to process oxidized pyrimidines in DNA. We demonstrate that Ntg1 has (O)G-specific glycosylase/lyase activity indistinguishable from that of yOgg2, Targeted disruption of the NTG 1 gene resulted in complete loss of yOgg2 activity and yeast lacking NTG1 had an elevated rate of A:T to C:G transversions.Conclusions: The Ntg1 and yOgg2 activities are encoded by a single gene. We propose that yOgg2 has evolved to process (O)G:A mis-pairs that have arisen through mis-incorporation of 8-oxo-dGTP during replication. Thus, the GO system in S. cerevisiae is fundamentally distinct from that in bacteria and mammals.