A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex
A molecular mechanism for DNA damage recognition by the xeroderma pigmentosum group C protein complex
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DOI：
10.1016/s1568-7864(01)00008-8
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发表时间：
2002-01-22
期刊：
影响因子：
3.8
通讯作者：
Hanaoka, F
中科院分区：
文献类型：
--
作者：
Sugasawa, K;Shimizu, Y;Hanaoka, F
XPC-HR23B复合体参与DNA损伤识别和启动全基因组核苷酸切除修复(GG-NER)。我们以前的研究表明，XPC-HR23B识别并结合含有螺旋扭曲的DNA，而无论是否存在受损的碱基。在这里，我们描述了使用各种定义的DNA底物对XPC-HR23B的DNA结合特异性的扩展分析。虽然XPC-HR23B对单链DNA的亲和力明显高于双链DNA，但DNA的特殊二级结构，包括单链和双链连接，强烈倾向于该复合体。这表明，双链DNA中不能形成正常Watson-Crick碱基对的碱基的存在是决定XPC-HR23B结合特异性的关键因素。使用环状DNA底物的DNase I足迹分析表明，单个XPC-HR23B复合体以不对称的方式保护扭曲的位点，与首选的二级结构一致。XPC-HR23B的特异性结合无疑是一个重要的分子过程，在此基础上，NER机制可以检测到DNA修复过程中化学结构不同的各种损伤。(C)2002 Elsevier Science B.V.保留所有权利。
The XPC-HR23B complex is involved in DNA damage recognition and the initiation of global genomic nucleotide excision repair (GG-NER). Our previous studies demonstrate that XPC-HR23B recognizes and binds DNA containing a helix distortion, regardless of the presence or absence of damaged bases. Here, we describe an extended analysis of the DNA binding specificity of XPC-HR23B using various defined DNA substrates. Although XPC-HR23B showed significantly higher affinity for single-stranded DNA than double-stranded DNA, specific secondary structures of DNA, involving a single- and double-strand junction, were strongly preferred by the complex. This indicates that the presence of bases, which cannot form normal Watson-Crick base pairs in double-stranded DNA, is a critical factor in determining the specificity of XPC-HR23B binding. A DNase I footprint analysis, using a looped DNA substrate, revealed that a single XPC-HR23B complex protected a distorted site in an asymmetrical manner, consistent with the preferred secondary structure. The specific binding of XPC-HR23B is undoubtedly an important molecular process, based on which NER machinery detects a wide variety of lesions that vary in terms of chemical structure during DNA repair. (C) 2002 Elsevier Science B.V. All rights reserved.