8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1.
8-Oxo-7,8-dihydroguanine in DNA does not constitute a barrier to transcription, but is converted into transcription-blocking damage by OGG1.
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DOI：
10.1093/nar/gkr163
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发表时间：
2011-08
影响因子：
14.9
通讯作者：
Khobta A
中科院分区：
文献类型：
--
作者：
Kitsera N;Stathis D;Lühnsdorf B;Müller H;Carell T;Epe B;Khobta A
常见的DNA碱基修饰8-氧代-7，8-二氢鸟嘌呤(8-oxo-G)影响转录的效率和保真度。我们构建了携带单个8-oxo-G残基的质粒底物，特异性地定位在转录或非转录的DNA链上，以研究它们对EGFP报告基因表达的影响，并探讨碱基切除修复在转录抑制机制中的作用。我们报道，8-oxo-G不直接阻断细胞中的转录，因为在转录的DNA链中，单个8-oxo-G并不降低修复缺陷(OGG1-空)小鼠胚胎成纤维细胞系中EGFP的表达水平。相反，8-oxo-G对转录的抑制完全依赖于8-oxoguanine DNA糖基酶(OGG1)，同时不需要损伤在转录的DNA链中的定位。我们认为转录中断是由碱基切除修复中间体诱导的，因此，可能是各种DNA碱基修饰的共同结果。一致地，非阻断DNA修饰尿嘧啶也被发现抑制转录，但以不依赖于OGG1的方式。
The common DNA base modification 8-oxo-7,8-dihydroguanine (8-oxo-G) affects the efficiency and fidelity of transcription. We constructed plasmid substrates carrying single 8-oxo-G residues, specifically positioned in the transcribed or the non-transcribed DNA strands, to investigate their effects on the expression of an EGFP reporter gene and to explore the role of base excision repair in the mechanism of transcription inhibition. We report that 8-oxo-G does not directly block transcription in cells, since a single 8-oxo-G in the transcribed DNA strand did not reduce the EGFP expression levels in repair-deficient (OGG1-null) mouse embryonic fibroblast cell lines. Rather, inhibition of transcription by 8-oxo-G fully depends on 8-oxoguanine DNA glycosylase (OGG1) and, at the same time, does not require the localization of the lesion in the transcribed DNA strand. We propose that the interruption of transcription is induced by base excision repair intermediates and, therefore, could be a common consequence of various DNA base modifications. Concordantly, the non-blocking DNA modification uracil was also found to inhibit transcription, but in an OGG1-independent manner.
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影响因子：
3.8
作者：
Khobta, Andriy;Kitsera, Nataliya;Epe, Bernd
通讯作者：
Epe, Bernd
影响因子：
64.8
作者：
Maga, Giovanni;Villani, Giuseppe;Huebscher, Ulrich
通讯作者：
Huebscher, Ulrich
影响因子：
5.3
作者：
Kim, Nayun;Jinks-Robertson, Sue
通讯作者：
Jinks-Robertson, Sue
DOI：
10.1073/pnas.94.15.8010
发表时间：
1997-07-22
影响因子：
11.1
作者：
Radicella, JP;Dherin, C;Boiteux, S
通讯作者：
Boiteux, S
影响因子：
14.9
作者：
Khobta, Andriy;Anderhub, Simon;Epe, Bernd
通讯作者：
Epe, Bernd