Bacterial Global Regulators DksA/ppGpp Increase Fidelity of Transcription

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2015 Jan 22

PMID 25605801

Citations 39

Authors

Mohammad Roghanian

Nikolay Zenkin

Yulia Yuzenkova

Affiliations

Soon will be listed here.

Abstract

Collisions between paused transcription elongation complexes and replication forks inevitably happen, which may lead to collapse of replication fork and could be detrimental to cells. Bacterial transcription factor DksA and its cofactor alarmone ppGpp were proposed to contribute to prevention of such collisions, although the mechanism of this activity remains elusive. Here we show that DksA/ppGpp do not destabilise transcription elongation complexes or inhibit their backtracking, as was proposed earlier. Instead, we show, both in vitro and in vivo, that DksA/ppGpp increase fidelity of transcription elongation by slowing down misincorporation events. As misincorporation events cause temporary pauses, contribution to fidelity suggests the mechanism by which DksA/ppGpp contribute to prevention of collisions of transcription elongation complexes with replication forks. DksA is only the second known accessory factor, after transcription factor Gre, that increases fidelity of RNA synthesis in bacteria.

Citing Articles

Transcription-translation coupling: Recent advances and future perspectives.

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When push comes to shove - RNA polymerase and DNA-bound protein roadblocks.

Hao N, Donnelly A, Dodd I, Shearwin K Biophys Rev. 2023; 15(3):355-366.

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Transcription-Replication Collisions and Chromosome Fragility.

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The ancestral stringent response potentiator, DksA has been adapted throughout evolution to orchestrate the expression of metabolic, motility, and virulence pathways.

Cohen H, Adani B, Cohen E, Piscon B, Azriel S, Desai P Gut Microbes. 2021; 14(1):1997294.

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The Alarmone (p)ppGpp Regulates Primer Extension by Bacterial Primase.

Giramma C, DeFoer M, Wang J J Mol Biol. 2021; 433(19):167189.

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