人淋巴细胞中8-氧鸟嘌呤DNA糖基酶1 (OGG1)的DNA修复活性不依赖于基因多态性Ser326/Cys326

Kai Janssen , Kirsten Schlink , Walter Götte , Birgit Hippler , Bernd Kaina , Franz Oesch
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引用次数: 128

摘要

8-氧鸟嘌呤DNA糖基化酶1 (OGG1)是一种DNA修复酶,从DNA中去除7,8-二氢-8-氧鸟嘌呤(8oxoG)。由于8oxoG是一种高度错配病变,OGG1表达水平的降低可能导致更高的背景突变频率,并可能增加氧化应激个体的癌症风险。为了分析OGG1的自然变异,我们用含8oxog的寡核苷酸测定法测定了健康人淋巴细胞的DNA修复活性。获得的数据显示,淋巴细胞中OGG1活性的个体间差异为两倍。性别和吸烟行为对OGG1活性没有影响。转录分析显示,OGG1在淋巴细胞中表达了两个亚型1a和b。人类OGG1 (hOGG1)基因的结构分析显示,在高加索人群中存在Ser326/Cys326多态性,Ser326和Cys326的等位基因频率分别为75%和25%。这种多态性与OGG1活性的改变无关。所描述的用于测量低温保存淋巴细胞中OGG1活性的常规测试系统提供了高度可重复性的结果,并且是与氧化DNA损伤修复改变相关的风险评估的有用工具。
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DNA repair activity of 8-oxoguanine DNA glycosylase 1 (OGG1) in human lymphocytes is not dependent on genetic polymorphism Ser326/Cys326

8-Oxoguanine DNA glycosylase 1 (OGG1) is a DNA repair enzyme that excises 7,8-dihydro-8-oxoguanine (8oxoG) from DNA. Since 8oxoG is a highly mispairing lesion, decreased OGG1 expression level could lead to a higher background mutation frequency and could possibly increase the cancer risk of an individual under oxidative stress. In order to analyse the natural variation of OGG1, we measured the DNA repair activity in human lymphocytes of healthy individuals by means of an 8oxoG-containing oligonucleotide assay. The data obtained revealed a two fold interindividual variation of OGG1 activity in lymphocytes. There was no difference in OGG1 activity due to gender and smoking behaviour. Transcriptional analyses of OGG1 showed the expression of two isoforms, 1a and b, in lymphocytes. Structural analysis of the human OGG1 (hOGG1) gene revealed a Ser326/Cys326 polymorphism in the Caucasian population with allele frequencies of 75% for Ser326 and 25% for Cys326. This polymorphism was not associated with altered OGG1 activity. The described routine test system for measuring OGG1 activity in cryopreserved lymphocytes provided highly reproducible results and is a useful tool for risk assessment associated with alterations in the repair of oxidative DNA damage.

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