Manganese is Required for the Rapid Recovery of DNA Synthesis Following Oxidative Challenge in Escherichia coli
This study was supported by National Science Foundation grant MCB1916625.
Journal Of Bacteriology
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.
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Hutfilz, C. R., Wang, N. E., Hoff, C. A., Lee, J. A., Hackert, B. J., Courcelle, J., & Courcelle, C. T. (2019). Manganese is required for the rapid recovery of DNA synthesis following oxidative challenge in Escherichia coli. Journal Of Bacteriology, 201(4), 1-14.