Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis
Damage of zinc fingers in DNA repair proteins, a novel molecular mechanism in carcinogenesis
复制标题
DOI：
10.1016/j.toxlet.2005.10.018
复制
发表时间：
2006-03-15
影响因子：
3.5
通讯作者：
Bal, W
中科院分区：
文献类型：
--
作者：
Witkiewicz-Kucharczyk, A;Bal, W
锌指基序参与许多蛋白质组的蛋白质-核酸和蛋白质-蛋白质相互作用，包括那些参与DNA修复的蛋白质。锌（II）离子以四面体形式与半胱氨酸硫酸盐和/或组氨酸咪唑基团结合，维持了三维结构，这对结构域的功能至关重要。因此，锌指可以通过用另一种金属离子取代Zn（II）或由于硫代酸盐供体氧化而释放Zn（II）而受到损害。后者可能是氧化活性金属或其他氧化剂作用的结果。细胞培养和离体研究表明，确定的致癌金属和类金属的可溶性化合物，如砷、镉和镍，以及推定的致癌物，包括钴和铅，抑制含有DNA修复蛋白的锌指。进一步的实验表明，这些金属以及内源性氧化物质，包括过氧化氢、亚硝基谷胱甘肽和可还原硒化合物，会破坏或扭曲锌指结构域。因此，这种反应性可以被认为是一种新的致癌分子机制。2005爱思唯尔爱尔兰有限公司版权所有。
Zinc finger motifs participate in protein-nucleic acid and protein-protein interactions in many groups of proteins, including those involved in DNA repair. The Zn(II) ion, bonded tetrahedrally to cysteine thiolates and/or histidine imidazole groups, maintains the three-dimensional Structure, crucial for the function of the domain. Zinc fingers can thus be compromised by a substitution of Zn(II) with another metal ion or by a release of Zn(II), due to the oxidation of thiolate donors. The latter may result from an action of redox-active metals or other oxidative agents. Studies in cell Cultures and ex vivo demonstrated that Soluble compounds of definite carcinogenic metals and metalloids, such as arsenic, cadmium and nickel, and putative carcinogens, including cobalt and lead, inhibit zinc finger containing DNA repair proteins. Further experiments demonstrated that these metals, as well as endogeneous oxidative substances, including hydrogen peroxide, nitrosoglutathione, and reducible selenium compounds damage or distort zinc finger domains. This reactivity can therefore be regarded as a novel molecular mechanism in carcinogenesis. (c) 2005 Elsevier Ireland Ltd. All rights reserved.