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Cobalt and nickel impair DNA metabolism by the oxidative stress independent pathway
Metallomics ( IF 2.9 ) Pub Date : 2017-10-12 00:00:00 , DOI: 10.1039/c7mt00231a
Vineet Kumar 1, 2, 3, 4 , Rajesh Kumar Mishra 1, 2, 3, 4 , Gursharan Kaur 1, 2, 3, 4 , Dipak Dutta 1, 2, 3, 4
Affiliation  

The oxidative stress evolved under cobalt and nickel exposures is thought to exert toxicity, though the exact routes of such metal poisoning remain ambiguous. We revisited the metal toxicity in Escherichia coli to show that the cobalt and nickel exposures as low as 0.5 and 1mM levels, respectively, visibly inhibit growth. We also observed that acidic conditions aggravated, while alkaline conditions alleviated the metal toxicity. Besides, 1mM manganese, which is non-cytotoxic, as judged by the growth of E. coli, synergistically elevated cobalt and nickel stress. However, the metal toxicity did not lead to oxidative stress in E. coli. On the other hand, we show that cobalt and nickel, but not manganese, reduced the rate of DNA replication to 50% within 2 hours. Interestingly, the metal ions promoted DNA double-strand breaks but did not induce SOS repair pathways, indicating that the metal ions could block SOS induction. To test this, we show that cobalt and nickel, but not manganese, suppressed nalidixic acid-induced SOS response. Finally, using an in vitro assay system, we demonstrated that cobalt and nickel inhibit RecBCD function, which is essential for SOS induction. Therefore, our data indicate that cobalt and nickel affect DNA replication, damage DNA, and inhibit SOS repair pathway to exert toxicity.

中文翻译:

钴和镍通过不依赖氧化应激的途径损害DNA代谢

尽管这种金属中毒的确切途径仍然不明确,但在暴露于钴和镍的情况下产生的氧化应激被认为具有毒性。我们重新审视了大肠杆菌中的金属毒性,以表明分别低至0.5和1mM的钴和镍暴露明显抑制了生长。我们还观察到酸性条件加剧了,而碱性条件减轻了金属的毒性。此外,根据大肠杆菌的生长判断,无细胞毒性的1mM锰可协同增加钴和镍的胁迫。但是,金属毒性并未在大肠杆菌中导致氧化应激。另一方面,我们显示钴和镍(而不是锰)在2小时内将DNA复制的速率降低到50%。有趣的是,金属离子促进了DNA双链断裂,但没有诱导SOS修复途径,这表明金属离子可以阻止SOS的诱导。为了测试这一点,我们表明钴和镍而不是锰抑制了萘啶酸诱导的SOS反应。最后,使用体外测定系统,我们证明了钴和镍抑制RecBCD功能,这对于SOS诱导至关重要。因此,我们的数据表明钴和镍会影响DNA复制,破坏DNA并抑制SOS修复途径产生毒性。这对于SOS诱导至关重要。因此,我们的数据表明钴和镍会影响DNA复制,破坏DNA并抑制SOS修复途径产生毒性。这对于SOS诱导至关重要。因此,我们的数据表明钴和镍会影响DNA复制,破坏DNA并抑制SOS修复途径产生毒性。
更新日期:2017-10-12
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