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Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis

Transcription-induced mutagenic mechanisms limit genetic changes to times when expression happens and to coding DNA. It has been hypothesized that intrinsic sequences that have the potential to form alternate DNA structures, such as non-B DNA structures, influence these mechanisms. Non-B DNA structu...

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Autores principales: Ermi, Tatiana, Vallin, Carmen, García, Ana Gabriela Regalado, Bravo, Moises, Cordero, Ismaray Fernandez, Martin, Holly Anne, Pedraza-Reyes, Mario, Robleto, Eduardo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231525/
https://www.ncbi.nlm.nih.gov/pubmed/34204686
http://dx.doi.org/10.3390/microorganisms9061284
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author Ermi, Tatiana
Vallin, Carmen
García, Ana Gabriela Regalado
Bravo, Moises
Cordero, Ismaray Fernandez
Martin, Holly Anne
Pedraza-Reyes, Mario
Robleto, Eduardo
author_facet Ermi, Tatiana
Vallin, Carmen
García, Ana Gabriela Regalado
Bravo, Moises
Cordero, Ismaray Fernandez
Martin, Holly Anne
Pedraza-Reyes, Mario
Robleto, Eduardo
author_sort Ermi, Tatiana
collection PubMed
description Transcription-induced mutagenic mechanisms limit genetic changes to times when expression happens and to coding DNA. It has been hypothesized that intrinsic sequences that have the potential to form alternate DNA structures, such as non-B DNA structures, influence these mechanisms. Non-B DNA structures are promoted by transcription and induce genome instability in eukaryotic cells, but their impact in bacterial genomes is less known. Here, we investigated if G4 DNA- and hairpin-forming motifs influence stationary-phase mutagenesis in Bacillus subtilis. We developed a system to measure the influence of non-B DNA on B. subtilis stationary-phase mutagenesis by deleting the wild-type argF at its chromosomal position and introducing IPTG-inducible argF alleles differing in their ability to form hairpin and G4 DNA structures into an ectopic locus. Using this system, we found that sequences predicted to form non-B DNA structures promoted mutagenesis in B. subtilis stationary-phase cells; such a response did not occur in growing conditions. We also found that the transcription-coupled repair factor Mfd promoted mutagenesis at these predicted structures. In summary, we showed that non-B DNA-forming motifs promote genetic instability, particularly in coding regions in stressed cells; therefore, non-B DNA structures may have a spatial and temporal mutagenic effect in bacteria. This study provides insights into mechanisms that prevent or promote mutagenesis and advances our understanding of processes underlying bacterial evolution.
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spelling pubmed-82315252021-06-26 Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis Ermi, Tatiana Vallin, Carmen García, Ana Gabriela Regalado Bravo, Moises Cordero, Ismaray Fernandez Martin, Holly Anne Pedraza-Reyes, Mario Robleto, Eduardo Microorganisms Article Transcription-induced mutagenic mechanisms limit genetic changes to times when expression happens and to coding DNA. It has been hypothesized that intrinsic sequences that have the potential to form alternate DNA structures, such as non-B DNA structures, influence these mechanisms. Non-B DNA structures are promoted by transcription and induce genome instability in eukaryotic cells, but their impact in bacterial genomes is less known. Here, we investigated if G4 DNA- and hairpin-forming motifs influence stationary-phase mutagenesis in Bacillus subtilis. We developed a system to measure the influence of non-B DNA on B. subtilis stationary-phase mutagenesis by deleting the wild-type argF at its chromosomal position and introducing IPTG-inducible argF alleles differing in their ability to form hairpin and G4 DNA structures into an ectopic locus. Using this system, we found that sequences predicted to form non-B DNA structures promoted mutagenesis in B. subtilis stationary-phase cells; such a response did not occur in growing conditions. We also found that the transcription-coupled repair factor Mfd promoted mutagenesis at these predicted structures. In summary, we showed that non-B DNA-forming motifs promote genetic instability, particularly in coding regions in stressed cells; therefore, non-B DNA structures may have a spatial and temporal mutagenic effect in bacteria. This study provides insights into mechanisms that prevent or promote mutagenesis and advances our understanding of processes underlying bacterial evolution. MDPI 2021-06-12 /pmc/articles/PMC8231525/ /pubmed/34204686 http://dx.doi.org/10.3390/microorganisms9061284 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ermi, Tatiana
Vallin, Carmen
García, Ana Gabriela Regalado
Bravo, Moises
Cordero, Ismaray Fernandez
Martin, Holly Anne
Pedraza-Reyes, Mario
Robleto, Eduardo
Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis
title Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis
title_full Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis
title_fullStr Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis
title_full_unstemmed Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis
title_short Non-B DNA-Forming Motifs Promote Mfd-Dependent Stationary-Phase Mutagenesis in Bacillus subtilis
title_sort non-b dna-forming motifs promote mfd-dependent stationary-phase mutagenesis in bacillus subtilis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8231525/
https://www.ncbi.nlm.nih.gov/pubmed/34204686
http://dx.doi.org/10.3390/microorganisms9061284
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