Transcriptional mutagenesis induced by uracil and 8-oxoguanine in Escherichia coli
Transcriptional mutagenesis induced by uracil and 8-oxoguanine in Escherichia coli
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DOI：
10.1016/s1097-2765(03)00360-5
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发表时间：
2003-10-01
期刊：
影响因子：
16
通讯作者：
Doetsch, PW
中科院分区：
文献类型：
--
作者：
Brégeon, D;Doddridge, ZA;Doetsch, PW
在自然环境中暴露于DNA损伤剂的细胞不会经历连续的复制循环，但更频繁地参与基因转录。荧光素酶基因表达分析与DNA模板含有尿嘧啶或8-氧代鸟嘌呤，放置在一个确定的位置，表明在nondividing大肠杆菌细胞，有效的诱变损伤旁路在体内转录过程中发生。转录本群体的序列分析显示，RNA聚合酶插入腺嘌呤相对于尿嘧啶，和腺嘌呤或胞嘧啶相对于8-氧代鸟嘌呤。令人惊讶的是，缺失也检测到8-氧代鸟嘌呤含有模板，表明RNA聚合酶在此病变滑动。遗传分析表明，在大肠杆菌中，8-氧代鸟嘌呤受到转录偶联修复。因此，DNA损伤改变了体内转录的保真度，这可能导致突变蛋白的产生，这些突变蛋白有可能改变非分裂细胞的表型。
Cells exposed to DNA damaging agents in their natural environment do not undergo continuous cycles of replication but are more frequently engaged in gene transcription. Luciferase gene expression analysis with DNA templates containing uracil or 8-oxoguanine, placed at a defined position, indicated that in nondividing Escherichia coli cells, efficient mutagenic lesion bypass does occur in vivo during transcription. Sequence analyses of the transcript population revealed that RNA polymerase inserts adenine opposite to uracil, and adenine or cytosine opposite to 8-oxoguanine. Surprisingly, deletions were also detected for 8-oxoguanine-containing templates, indicating RNA polymerase slippage over this lesion. Genetic analyses showed that, in E coli, 8-oxoguanine is subject to transcription-coupled repair. Consequently, DNA damages alter transcription fidelity in vivo, which may lead to the production of mutant proteins that have the potential to change the phenotype of nondividing cells.