Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases - Archive ouverte HAL
Article Dans Une Revue Genes Année : 2023

Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases

Virali Parekh
  • Fonction : Auteur
South Dakota School of Mines and Technology
Grzegorz Węgrzyn
University of Gdańsk
Véronique Arluison
LLB - Matière molle et biophysique
Richard Sinden
South Dakota School of Mines and Technology

Résumé

Guanine-rich DNA can fold into highly stable four-stranded DNA structures called G-quadruplexes (G4). Originally identified in sequences from telomeres and oncogene promoters, they can alter DNA metabolism. Indeed, G4-forming sequences represent obstacles for the DNA polymerase, with important consequences for cell life as they may lead to genomic instability. To understand their role in bacterial genomic instability, different G-quadruplex-forming repeats were cloned into an Escherichia coli genetic system that reports frameshifts and complete or partial deletions of the repeat when the G-tract comprises either the leading or lagging template strand during replication. These repeats formed stable G-quadruplexes in single-stranded DNA but not naturally supercoiled double-stranded DNA. Nevertheless, transcription promoted G-quadruplex formation in the resulting R-loop for (G3T)4 and (G3T)8 repeats. Depending on genetic background and sequence propensity for structure formation, mutation rates varied by five orders of magnitude. Furthermore, while in vitro approaches have shown that bacterial helicases can resolve G4, it is still unclear whether G4 unwinding is important in vivo. Here, we show that a mutation in recG decreased mutation rates, while deficiencies in the structure-specific helicases DinG and RecQ increased mutation rates. These results suggest that G-quadruplex formation promotes genetic instability in bacteria and that helicases play an important role in controlling this process in vivo.

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Sciences du Vivant [q-bio]

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https://hal.science/hal-04353211

Soumis le : mardi 19 décembre 2023-12:53:37

Dernière modification le : vendredi 19 avril 2024-11:50:09

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hal-04353211 , version 1 (19-12-2023)

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Virali Parekh, Grzegorz Węgrzyn, Véronique Arluison, Richard Sinden. Genomic Instability of G-Quadruplex Sequences in Escherichia coli: Roles of DinG, RecG, and RecQ Helicases. Genes, 2023, 14 (9), pp.1720. ⟨10.3390/genes14091720⟩. ⟨hal-04353211⟩

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