Myka, Kamila Katarzyna, Hawkins, Michelle orcid.org/0000-0001-9393-8206, Syeda, Aisha H orcid.org/0000-0003-3201-4135 et al. (6 more authors) (2017) Inhibiting translation elongation can aid genome duplication in Escherichia coli. Nucleic Acids Research. pp. 2571-2584. ISSN 0305-1048
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | ©The Author(s) 2016. |
Keywords: | 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 |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Biology (York) |
Depositing User: | Pure (York) |
Date Deposited: | 09 Dec 2016 09:32 |
Last Modified: | 02 Apr 2025 23:08 |
Published Version: | https://doi.org/10.1093/nar/gkw1254 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1093/nar/gkw1254 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:109285 |
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