Repair of 8-oxoG is slower in endogenous nuclear genes than in mitochondrial DNA and is without strand bias
Repair of 8-oxoG is slower in endogenous nuclear genes than in mitochondrial DNA and is without strand bias
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DOI：
10.1016/s1568-7864(02)00003-4
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发表时间：
2002-04-29
期刊：
影响因子：
3.8
通讯作者：
Stevnsner, T
中科院分区：
文献类型：
--
作者：
Thorslund, T;Sunesen, M;Stevnsner, T
DNA容易受到某些氧自由基的攻击，形成的主要DNA损伤之一是7，8-二氢-8-氧代鸟嘌呤（8-oxoG），这是一种高度致突变的损伤，可以与腺嘌呤错配。通过测量用光敏剂Ro 19 -8022处理中国仓鼠卵巢（CHO）成纤维细胞后8-oxoG的基因特异性去除来研究8-oxoG的修复。该化合物引入8-oxoG损伤，然后可以用大肠杆菌甲酰氨基嘧啶DNA糖基化酶（FPG）检测。在本报告中，我们提出了对位于不同重要细胞区域的内源基因的基因特异性修复分析，以及对内源基因中8-oxoG的链特异性DNA修复的首次分析。与非转录区相比，我们不能检测到转录基因的任何优先修复，并且我们在管家基因二氢叶酸还原酶（DHFR）的修复中没有检测到任何链偏差。在体内，线粒体DNA是高度暴露于活性氧（ROS），我们发现，8-oxoG的修复是更有效的线粒体DNA比在核DNA。(C)2002 Elsevier Science B. V.保留所有权利。
DNA is vulnerable to the attack of certain oxygen radicals and one of the major DNA lesions formed is 7,8-dihydro-8-oxoguanine (8-oxoG), a highly mutagenic lesion that can mispair with adenine. The repair of 8-oxoG was studied by measuring the gene specific removal of 8-oxoG after treatment of Chinese hamster ovary (CHO) fibroblasts with the photosensitizer Ro19-8022. This compound introduces 8-oxoG lesions, which can then be detected with the Escherichia coli formamidopyrimidine DNA glycosylase (FPG). In this report we present gene specific repair analysis of endogenous genes situated in different important cellular regions and also the first analysis of strand specific DNA repair of 8-oxoG in an endogenous gene. We were not able to detect any preferential repair of transcribed genes compared to non-transcribed regions and we did not detect any strand-bias in the repair of the housekeeping gene, dihydrofolate reductase (DHFR). In vivo, mitochondrial DNA is highly exposed to reactive oxygen species (ROS), and we find that the repair of 8-oxoG is more efficient in the mitochondrial DNA than in the nuclear DNA. (C) 2002 Elsevier Science B.V. All rights reserved.