Interference by toxic metal compounds with isolated zinc finger DNA repair proteins
Interference by toxic metal compounds with isolated zinc finger DNA repair proteins
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DOI：
10.1016/s0378-4274(99)00273-8
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发表时间：
2000-03-15
影响因子：
3.5
通讯作者：
Hartwig, A
中科院分区：
文献类型：
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作者：
Asmuss, M;Mullenders, LHF;Hartwig, A
镍、镉、钴和砷的化合物先前已显示在低浓度下抑制DNA修复过程。在本研究中，我们调查是否这种修复抑制可能是由锌的DNA修复蛋白的锌指结构的位移。作为模型，应用细菌甲酰胺嘧啶-DNA糖基化酶（Fpg）和哺乳动物XPA蛋白。这两种蛋白质被抑制镉（II）和铜（II）。Hg（II）强烈抑制Fpg蛋白，但不影响XPA蛋白。相反，XPA蛋白被Co（II）和Ni（II）干扰，而Fpg蛋白的活性没有降低。As（III）和Pb（II）均不能抑制蛋白质的表达。因此，每个锌指蛋白似乎都有自己的结构特征和对有毒金属离子的敏感性。此外，每种金属都发挥特定的机制，导致DNA修复抑制。(C)2000由Elsevier Science爱尔兰有限公司出版。保留所有权利。
Compounds of nickel, cadmium, cobalt and arsenic have been shown previously to inhibit DNA repair processes at low concentrations. In the present study we investigated whether this repair inhibition may be caused by the displacement of zinc in zinc finger structures of DNA repair proteins. As models, the bacterial formamidopyrimidine-DNA glycosylase (Fpg) and the mammalian XPA protein were applied. Both proteins were inhibited by Cd(II) and Cu(II). Hg(II) strongly inhibited the Fpg protein, but did not affect the XPA protein. In contrast, the XPA protein was disturbed by Co(II) and Ni(II), while the activity of the Fpg protein was not reduced. Neither protein was inhibited by As(III) or Pb(II). Thus, each zinc finger protein appears to have its own structural features and sensitivities towards toxic metal ions. Furthermore, each metal exerts specific mechanisms leading to DNA repair inhibition. (C) 2000 Published by Elsevier Science Ireland Ltd. All rights reserved.