Manganese Is Required for the Rapid Recovery of DNA Synthesis following Oxidative Challenge in Escherichia coli
Manganese Is Required for the Rapid Recovery of DNA Synthesis following Oxidative Challenge in Escherichia coli
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DOI：
10.1128/jb.00426-19
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发表时间：
2019-12-01
影响因子：
3.2
通讯作者：
Courcelle, Charmain T.
中科院分区：
文献类型：
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作者：
Hutfilz, Corinne R.;Wang, Natalie E.;Courcelle, Charmain T.
二价金属如铁和锰在细胞对氧化挑战的反应中起重要作用，并且是许多酶所需的辅因子。然而，这些金属如何影响氧化挑战后的复制是未知的。在这里，我们表明，在大肠杆菌中的复制被抑制后的挑战与过氧化氢，并需要锰的DNA合成的快速恢复。我们发现，锰依赖的DNA合成恢复发生独立的损伤修复，适度提高细胞存活率，并与诱变率升高。锰依赖性诱变涉及复制和translesion聚合酶，并需要事先中断过氧化氢发生。综合以上研究结果，我们认为E.大肠杆菌可能利用在氧化挑战期间被氧化和失活的铁依赖性酶。这些数据表明，锰remetallates这些或替代酶，使基因组DNA复制恢复，虽然降低fidelity.IMPORTANCE铁和锰发挥重要作用，在细胞如何科普氧应激。然而，这些金属如何影响细胞在氧化挑战后的复制能力尚不清楚。在这里，我们表明，在大肠杆菌中的复制被抑制后的挑战与过氧化氢，并需要锰的DNA合成的快速恢复。锰依赖的DNA合成恢复独立于损伤修复发生，并适度提高生存率，但它也增加了细胞中的突变率。结果表明，E. Colt可能利用在氧化挑战期间被氧化和失活的铁依赖性酶。我们建议，锰remetallates这些或替代酶，使基因组DNA复制恢复，虽然保真度降低。
Divalent metals such as iron and manganese play an important role in the cellular response to oxidative challenges and are required as cofactors by many enzymes. However, how these metals affect replication after oxidative challenge is not known. Here, we show that replication in Escherichia coli is inhibited following a challenge with hydrogen peroxide and requires manganese for the rapid recovery of DNA synthesis. We show that the manganese-dependent recovery of DNA synthesis occurs independent of lesion repair, modestly improves cell survival, and is associated with elevated rates of mutagenesis. The Mn-dependent mutagenesis involves both replicative and translesion polymerases and requires prior disruption by H2O2 to occur. Taking these findings together, we propose that replication in E. coli is likely to utilize an iron-dependent enzyme(s) that becomes oxidized and inactivated during oxidative challenges. The data suggest that manganese remetallates these or alternative enzymes to allow genomic DNA replication to resume, although with reduced fidelity.IMPORTANCE Iron and manganese play important roles in how cell's cope with oxygen stress. However, how these metals affect the ability of cells to replicate after oxidative challenges is not known. Here, we show that replication in Escherichia coil is inhibited following a challenge with hydrogen peroxide and requires manganese for the rapid recovery of DNA synthesis. The manganese-dependent recovery of DNA synthesis occurs independently of lesion repair and modestly improves survival, but it also increases the mutation rate in cells. The results imply that replication in E. colt is likely to utilize an iron-dependent enzyme(s) that becomes oxidized and inactivated during oxidative challenges. We propose that manganese remetallates these or alternative enzymes to allow genomic DNA replication to resume, although with reduced fidelity.