A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex
A nucleobase lesion remodels the interaction of its normal neighbor in a DNA glycosylase complex
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DOI：
10.1073/pnas.0603644103
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发表时间：
2006-10-10
影响因子：
11.1
通讯作者：
Verdline, Gregory L.
中科院分区：
文献类型：
--
作者：
Banerjee, Anirban;Verdline, Gregory L.
DNA糖基化酶如何搜索数百万个碱基对，并区分罕见的损伤位点和其他未损伤的碱基，目前还知之甚少。更不了解的是DNA糖基化酶与未受损DNA相互作用产生的结构状态的细节。识别突变损伤7，8-二氢-8-氧代鸟嘌呤（8-oxoguanine，oxoG）是一个特别艰巨的挑战，因为这种氧化的核碱基与其正常的对应物鸟嘌呤（G）只有两个原子的区别，并且隐藏在裸露的B型DNA结构中，oxoG和G实际上彼此无法区分。我们已经使用二硫环交联技术捕获人oxoG修复蛋白，8-氧代鸟嘌呤DNA糖基化酶I（hOGG 1），其采样位于DNA中邻近oxoG：C碱基对的未受损的G：C碱基对。捕获的复合物的X射线结构揭示了8-oxoG的存在急剧改变了挤出的G的局部构象。在这种结构中，G的挤出但螺旋内的状态提供了一种在碱基挤出途径中的早期中间体的观点。
How DNA glycosylases search through millions of base pairs and discriminate between rare sites of damage and otherwise undamaged bases is poorly understood. Even less understood are the details of the structural states arising from DNA glycosylases interacting with undamaged DNA. Recognizing the mutagenic lesion 7,8-dihydro-8-oxoguanine (8-oxoguanine, oxoG) represents an especially formidable challenge, because this oxidized nucleobase differs by only two atoms from its normal counterpart, guanine (G), and buried in the structure of naked B-form DNA, oxoG and G are practically indistinguishable from each other. We have used disulfidcle cross-linking technology to capture a human oxoG repair protein, 8-oxoguanine DNA glycosylase I (hOGG1) sampling an undamaged G:C base pair located adjacent to an oxoG:C base pair in DNA. The x-ray structure of the trapped complex reveals that the presence of the 8-oxoG drastically changes the local conformation of the extruded G. The extruded but intrahelical state of the G in this structure offers a view of an early intermediate in the base-extrusion pathway.