Direct visualization of a DNA glycosylase searching for damage
Direct visualization of a DNA glycosylase searching for damage
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DOI：
10.1016/s1074-5521(02)00120-5
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发表时间：
2002-03-01
影响因子：
--
通讯作者：
Verdine, GL
中科院分区：
文献类型：
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作者：
Chen, LW;Haushalter, KA;Verdine, GL
DNA糖基化酶通过识别基因组中受损的碱基并催化其切除来保持遗传信息的完整性。目前还不清楚DNA糖基化酶如何在大量的正常碱基中定位隐藏在DNA螺旋中的共价修饰的碱基。在这里，我们采用原子力显微镜（AFM）与碳纳米管探针图像搜索人类8-氧代鸟嘌呤DNA糖基化酶（hOGG 1）扫描DNA的中间体。我们发现，hOGG 1询问DNA在未受损的网站诱导激烈的扭结。这些非病变特异性搜索中间体的尖锐DNA弯曲角与在含有8-氧代鸟嘌呤的DNA与hOGG 1结合的特定复合物中观察到的紧密匹配。这些发现表明，hOGG 1在寻找受损碱基时会主动扭曲DNA。
DNA glycosylases preserve the integrity of genetic information by recognizing damaged bases in the genome and catalyzing their excision. It is unknown how DNA glycosylases locate covalently modified bases hidden in the DNA helix amongst vast numbers of normal bases. Here we employ atomic-force microscopy (AFM) with carbon nanotube probes to image search intermediates of human 8-oxoguanine DNA glycosylase (hOGG1) scanning DNA. We show that hOGG1 interrogates DNA at undamaged sites by inducing drastic kinks. The sharp DNA bending angle of these non-lesion-specific search intermediates closely matches that observed in the specific complex of 8-oxoguanine-containing DNA bound to hOGG1. These findings indicate that hOGG1 actively distorts DNA while searching for damaged bases.