The Presence and Localization of G-Quadruplex Forming Sequences in the Domain of Bacteria

Bartas, Martin; Čutová, Michaela; Brázda, Václav; Kaura, Patrik; Šťastný, Jiří; Kolomazník, Jan; Coufal, Jan; Goswami, Pratik; Červeň, Jiří; Pečínka, Petr

doi:10.3390/molecules24091711

Cited by 80 publications

(78 citation statements)

References 61 publications

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“…They have been found to be regulatory elements in the human genome implicated in key functions such as telomere maintenance and genome transcription regulation, replication and repair (17). G4 structures have also been identified in fungi (18)(19)(20)(21), bacteria (22)(23)(24)(25)(26) and parasites (27)(28)(29)(30)(31)(32). Their occurrence are known in many viruses that afflict humans as well.…”

Section: Introductionmentioning

confidence: 99%

Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2

Belmonte-Reche

Serrano

González

et al. 2020

Preprint

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In this paper we report the analysis of the 2019-nCoV genome and related viruses using an upgraded version of the open-source algorithm G4-iM Grinder. This version improves the functionality of the software, including an easy way to determine the potential biological features affected by the candidates found. The quadruplex definitions of the algorithm were optimized for 2019-nCoV. Using a lax quadruplex definition ruleset, which accepts amongst other parameters two residue G- and C-tracks, hundreds of potential quadruplex candidates were discovered. These sequences were evaluated by their in vitro formation probability, their position in the viral RNA, their uniqueness and their conservation rates (calculated in over three thousand different COVID-19 clinical cases and sequenced at different times and locations during the ongoing pandemic). These results were compared sequentially to other Coronaviridae members, other Group IV (+)ssRNA viruses and the entire realm. Sequences found in common with other species were further analyzed and characterized. Sequences with high scores unique to the 2019-nCoV were studied to investigate the variations amongst similar species. Quadruplex formation of the best candidates was then confirmed experimentally. Using NMR and CD spectroscopy, we found several highly stable RNA quadruplexes that may be suitable theranostic targets against the 2019-nCoV.

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Section: Introductionmentioning

confidence: 99%

Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2

Belmonte-Reche

Serrano

González

et al. 2020

Preprint

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“…In humans, they can occur in immunoglobulin switch regions, oncogene promoters, the first introns of genes, and the 5' untranslated regions near translation start sites [4,5,7,12]. These sequences also occur in bacterial genomes [13][14][15][16][17]. Reports vary as to the assessment of the potential for the participation of G-quadruplex structures in the regulation of gene expression in E. coli [13,14,18,19].…”

Section: Introductionmentioning

confidence: 99%

Role of Hfq in Genome Evolution: Instability of G-Quadruplex Sequences in E. coli

et al. 2019

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Certain G-rich DNA repeats can form quadruplex in bacterial chromatin that can present blocks to DNA replication and, if not properly resolved, may lead to mutations. To understand the participation of quadruplex DNA in genomic instability in Escherichia coli (E. coli), mutation rates were measured for quadruplex-forming DNA repeats, including (G 3 T) 4 , (G 3 T) 8 , and a RET oncogene sequence, cloned as the template or nontemplate strand. We evidence that these alternative structures strongly influence mutagenesis rates. Precisely, our results suggest that G-quadruplexes form in E. coli cells, especially during transcription when the G-rich strand can be displaced by R-loop formation. Structure formation may then facilitate replication misalignment, presumably associated with replication fork blockage, promoting genomic instability. Furthermore, our results also evidence that the nucleoid-associated protein Hfq is involved in the genetic instability associated with these sequences. Hfq binds and stabilizes G-quadruplex structure in vitro and likely in cells. Collectively, our results thus implicate quadruplexes structures and Hfq nucleoid protein in the potential for genetic change that may drive evolution or alterations of bacterial gene expression. variable with strands arranged in a parallel, antiparallel, or mixed orientations associated with various glycosidic configurations of guanines [1,[3][4][5]. A single repeat motif can often form multiple structures depending on ionic conditions, as shown for repeats at human telomeres and oncogene promoters [4][5][6][7]. When G-quadruplex structures form in duplex DNA, the C-rich DNA strand complementary to G-quadruplex-forming sequences can form a four stranded i-motif at low pH [8], in which two tracts of cytosines form interdigitated C•C + base pairs [7,9,10] (Figure 1C).Microorganisms 2019, 7, x 2 of 16 quartets are stabilized by monovalent cations. The topology of quadruplex structures is highly variable with strands arranged in a parallel, antiparallel, or mixed orientations associated with various glycosidic configurations of guanines [1,[3][4][5]. A single repeat motif can often form multiple structures depending on ionic conditions, as shown for repeats at human telomeres and oncogene promoters [4][5][6][7]. When G-quadruplex structures form in duplex DNA, the C-rich DNA strand complementary to G-quadruplex-forming sequences can form a four stranded i-motif at low pH [8], in which two tracts of cytosines form interdigitated C•C + base pairs [7,9,10] (Figure 1C).

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“…A wide array of sequences have been shown to form quadruplexes, but longer G-tracts and shorter interruptions form more stable G-quadruplexes, although the size of the loop also impacts on the type of folding seen in stable quadruplexes [44]. Importantly, the likelihood of G-quadruplexes forming in genomes varies dramatically in different locations of DNA molecules [45]. For example, simple repeats that are rich in G bases are often found at telomeric ends of chromosomes and there is significant evidence that such sequences form complexes of proteins specifically bound to four-stranded structures [46].…”

Section: Dna Structures Formed By Dna Repeatsmentioning

confidence: 99%

Structures and stability of simple DNA repeats from bacteria

Brázda

Fojta

Bowater

2020

Biochemical Journal

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DNA is a fundamentally important molecule for all cellular organisms due to its biological role as the store of hereditary, genetic information. On the one hand, genomic DNA is very stable, both in chemical and biological contexts, and this assists its genetic functions. On the other hand, it is also a dynamic molecule, and constant changes in its structure and sequence drive many biological processes, including adaptation and evolution of organisms. DNA genomes contain significant amounts of repetitive sequences, which have divergent functions in the complex processes that involve DNA, including replication, recombination, repair, and transcription. Through their involvement in these processes, repetitive DNA sequences influence the genetic instability and evolution of DNA molecules and they are located non-randomly in all genomes. Mechanisms that influence such genetic instability have been studied in many organisms, including within human genomes where they are linked to various human diseases. Here, we review our understanding of short, simple DNA repeats across a diverse range of bacteria, comparing the prevalence of repetitive DNA sequences in different genomes. We describe the range of DNA structures that have been observed in such repeats, focusing on their propensity to form local, non-B-DNA structures. Finally, we discuss the biological significance of such unusual DNA structures and relate this to studies where the impacts of DNA metabolism on genetic stability are linked to human diseases. Overall, we show that simple DNA repeats in bacteria serve as excellent and tractable experimental models for biochemical studies of their cellular functions and influences.

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The Presence and Localization of G-Quadruplex Forming Sequences in the Domain of Bacteria

Cited by 80 publications

References 61 publications

Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2

Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2

Role of Hfq in Genome Evolution: Instability of G-Quadruplex Sequences in E. coli

Structures and stability of simple DNA repeats from bacteria

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