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Inhibiting translation elongation can aid genome duplication in Escherichia coli

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JournalNucleic Acids Research
DateAccepted/In press - 1 Dec 2016
DateE-pub ahead of print - 12 Dec 2016
DatePublished (current) - 17 Mar 2017
Issue number5
Volume45
Number of pages14
Pages (from-to)2571-2584
Early online date12/12/16
Original languageEnglish

Abstract

Conflicts between replication and transcription challenge chromosome duplication. Escherichia coli replisome movement along transcribed DNA is promoted by Rep and UvrD accessory helicases with Δrep ΔuvrD cells being inviable under rapid growth conditions. We have discovered that mutations in a tRNA gene, aspT, in an aminoacyl tRNA synthetase, AspRS, and in a translation factor needed for efficient proline-proline bond formation, EF-P, suppress Δrep ΔuvrD lethality. Thus replication-transcription conflicts can be alleviated by the partial sacrifice of a mechanism that reduces replicative barriers, namely translating ribosomes that reduce RNA polymerase backtracking. Suppression depends on RelA-directed synthesis of (p)ppGpp, a signalling molecule that reduces replication-transcription conflicts, with RelA activation requiring ribosomal pausing. Levels of (p)ppGpp in these suppressors also correlate inversely with the need for Rho activity, an RNA translocase that can bind to emerging transcripts and displace transcription complexes. These data illustrate the fine balance between different mechanisms in facilitating gene expression and genome duplication and demonstrate that accessory helicases are a major determinant of this balance. This balance is also critical for other aspects of bacterial survival: the mutations identified here increase persistence indicating that similar mutations could arise in naturally occurring bacterial populations facing antibiotic challenge.

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©The Author(s) 2016.

    Research areas

  • DNA Helicases, DNA Replication, Escherichia coli, Escherichia coli Proteins, Genome, Bacterial, Mutation, Peptide Chain Elongation, Translational, RNA, Transfer, Asp, Suppression, Genetic, Transfer RNA Aminoacylation, Journal Article

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