Duplex-tetraplex equilibria in guanine- and cytosine-rich DNA

Chalikian, Tigran V.; Liu, Lutan; Macgregor, Robert B.

doi:10.1016/j.bpc.2020.106473

Cited by 23 publications

(42 citation statements)

References 239 publications

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“…Therefore, the competition with a complementarity strand should play a major role in the formation and persistence of G4 structures in vivo , as recently pinpointed by Chalikian et al. ( 35 ). Two reports using single-molecule FRET or optical tweezers have shown that G4 can readily compete with the reannealing of dsDNA in vitro ( 44 , 45 ).…”

Section: Introductionmentioning

confidence: 87%

Folding and persistence times of intramolecular G-quadruplexes transiently embedded in a DNA duplex

Tran

Rieu

Hodeib

et al. 2021

Nucleic Acids Research

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G-quadruplex (G4) DNA structures have emerged as important regulatory elements during DNA metabolic transactions. While many in vitro studies have focused on the kinetics of G4 formation within DNA single-strands, G4 are found in vivo in double-stranded DNA regions, where their formation is challenged by the complementary strand. Since the energy of hybridization of Watson-Crick structures dominates the energy of G4 folding, this competition should play a critical role on G4 persistence. To address this, we designed a single-molecule assay allowing to measure G4 folding and persistence times in the presence of the complementary strand. We quantified both folding and unfolding rates of biologically relevant G4 sequences, such as the cMYC and cKIT oncogene promoters, human telomeres and an avian replication origin. We confirmed that G4s are found much more stable in tested replication origin and promoters than in human telomere repeats. In addition, we characterized how G4 dynamics was affected by G4 ligands and showed that both folding rate and persistence time increased. Our assay opens new perspectives for the measurement of G4 dynamics in double-stranded DNA mimicking a replication fork, which is important to understand their role in DNA replication and gene regulation at a mechanistic level.

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Section: Introductionmentioning

confidence: 87%

Folding and persistence times of intramolecular G-quadruplexes transiently embedded in a DNA duplex

Tran

Rieu

Hodeib

et al. 2021

Nucleic Acids Research

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“…Importantly, this is the first time that an intramolecular G4 formed by a long guanine stretches like the β A origin sequence was experimentally observed, since they tend to fold into intermolecular G4 structures (or a mixture of intra- and intermolecular structures) at the DNA concentrations required for common in vitro spectroscopic studies (10). This propensity to fold is unique among the sequences tested here and raises the possibility of the contribution of a i-motif forming on the opposite strand to the overall dynamics of the structure evidenced by our assay (35). Although analysis of i-motif formation is beyond the scope of the present study, our assay opens interesting avenues to assess the dynamics of its formation in slightly acidic buffers where its formation would be favored (71).…”

Section: Discussionmentioning

confidence: 82%

“…At the thermodynamic level, the energy of hybridization of a Watson-Crick duplex containing a G-rich DNA sequence is much larger (~50 kcal/mol) than the energy of G4 folding (~4-8 kcal/mol) (1). Therefore, the competition with a complementarity strand should play a major role in the formation and persistence of G4 structures in vivo, as recently pinpointed by Tigran & al (35). Two reports using single-molecule FRET or optical tweezers have shown that G4 can readily compete with the reannealing of dsDNA in vitro (44,45).…”

Section: Introductionmentioning

confidence: 93%

“…Their potential biological effect would require their persistence post replication in a context where they are embedded in a double-stranded DNA (dsDNA) bubble. Persistence of G4 structures within dsDNA is largely unknown, but may depend on their sequence, the genomic context and/or the presence of a bound protein (30)(31)(32)(33)(34)(35)(36). Convincing evidences of G4 formation in vivo have indeed been reported near several transcription start sites (37) or near-replication origins where G4 structures could participate in transient fork pausing or loading of proteins (10,11,38).…”

Section: Introductionmentioning

confidence: 99%

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Folding and Persistence Time of Intramolecular G-Quadruplexes Transiently Embedded in a DNA duplex

Tran

Rieu

Hodeib

et al. 2021

Preprint

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G-quadruplex (G4) DNA structures have emerged as important regulatory elements during DNA replication, transcription or repair. While many in-vitro studies have focused on the kinetics of G4 formation within DNA single-strands, G4 are found in-vivo in double-stranded DNA regions, where their formation is challenged by pairing between the two complementary strands. Since the energy of hybridization of Watson-Crick structures dominates the energy of G4 folding, this competition should play a critical role on the persistence of G4 in vivo. To address this issue, we designed a single molecule assay allowing measuring G4 folding and persistence while the structure is periodically challenged by the complementary strand. We quantified both the folding rate and the persistence time of biologically relevant G4 structures and showed that the dynamics of G4 formation depends strongly on the genomic location. G4 are found much more stable in promoter regions and replication origins than in telomeric regions. In addition, we characterized how G4 dynamics was affected by G4 ligands and showed that both folding rate and persistence increased. Our assay opens new perspectives for the measurement of G4 dynamics, which is critical to understand their role in genetic regulation.

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“…DNAs have been shown to play important roles in replication, transcription and translation. [13][14][15][16][17][18] DNA hairpins (DNA-Hp, Fig. 1A) regulate gene expression, act as target sites for protein recognition and nucleation sites for higher order RNA structures.…”

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confidence: 99%

Untangling the interaction of α-synuclein with DNA i-motifs and hairpins by volume-sensitive single-molecule FRET spectroscopy

et al. 2021

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Duplex-tetraplex equilibria in guanine- and cytosine-rich DNA

Cited by 23 publications

References 239 publications

Folding and persistence times of intramolecular G-quadruplexes transiently embedded in a DNA duplex

Folding and persistence times of intramolecular G-quadruplexes transiently embedded in a DNA duplex

Folding and Persistence Time of Intramolecular G-Quadruplexes Transiently Embedded in a DNA duplex

Untangling the interaction of α-synuclein with DNA i-motifs and hairpins by volume-sensitive single-molecule FRET spectroscopy

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