Chromium(III) bound to DNA templates promotes increased polymerase processivity and decreased fidelity during replication in vitro.
Chromium(III) bound to DNA templates promotes increased polymerase processivity and decreased fidelity during replication in vitro.
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与 DNA 模板结合的铬 (III) 可提高聚合酶的持续合成能力并降低体外复制过程中的保真度。
作者：
Snow,ET;Xu,LS
摘要：致癌铬[Cr (VI)]化合物在细胞内被还原为dna和蛋白反应性铬（III）。然而，铬（III）离子在铬致遗传毒性中的作用尚不清楚。我们在体外研究了铬（III）结合对DNA复制和聚合酶活性的影响。铬离子与DNA的结合缓慢且呈剂量依赖性。微摩尔浓度的游离铬抑制DNA复制，但如果通过凝胶过滤去除未结合的铬，则在铬结合模板上聚合酶I （Klenow片段）的DNA复制速率相对于对照增加了6倍以上。与此同时，处理能力提高了4倍，复制保真度降低了2倍。当极低浓度的铬离子与DNA结合时，这些效果是最佳的[每1000个核苷酸磷酸盐中有3-4个铬（III）离子]。铬浓度的增加导致DNA-DNA交联的产生和聚合酶活性的抑制。这些结果表明，低水平的DNA结合铬离子可能通过改变DNA复制的动力学和保真度来促进铬的突变和致癌作用。
Revised Manuscript Received July 26, 1991 abstract: Carcinogenic chromium [Cr (VI)] compounds are reduced intracellularly to DNA-and pro-tein-reactive chromium (III) species. However, the role of Cr (III) ions in chromium-induced genotoxicity remains unclear. We have investigated the effects of chromium (III) binding on DNA replication and polymerase processivity in vitro. Chromium ions bind slowly and in a dose-dependent manner to DNA.Micromolar concentrations of free chromium inhibit DNA replication, but if the unbound chromium is removed by gel filtration, the rate of DNA replication by polymerase I (Klenow fragment) on the chro-mium-bound template is increased greater than6-fold relative to the control. This increase is paralleled by as much as a 4-fold increase in processivity and a 2-fold decrease in replication fidelity. These effects are optimum when very low concentrations of chromium ions are bound to the DNA [3-4 Cr (III) ions per 1000 nucleotide phosphates]. Increased concentrations of chromium leadto the production of DNA-DNA cross-links and inhibition of polymerase activity. These results suggest that low levels of DNA-bound chromium (IIl) ions may contribute to chromium mutagenesis and carcinogenesis by altering the kinetics and fidelity of DNA replication.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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影响因子：
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