DNA-Directed Base Pair Opening

Timsit, Youri

doi:10.3390/molecules171011947

Cited by 6 publications

(5 citation statements)

References 55 publications

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“…However, their binding mechanism is poorly understood. As previously reported, DNA is a very fluctuant biopolymer with transient base pair openings ( 42 , 43 ), sufficiently dynamic to favor strand invasion of synthetic ONs. This requires typically high ON concentration ( 44 – 47 ) but due to the Hoogsteen-first binding, we expect bisLNAs to have superior ability to find their target along the plasmid, which enables binding at lower concentration.…”

Section: Discussionmentioning

confidence: 65%

Next-generation bis-locked nucleic acids with stacking linker and 2′-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes

et al. 2016

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Targeting and invading double-stranded DNA with synthetic oligonucleotides under physiological conditions remain a challenge. Bis-locked nucleic acids (bisLNAs) are clamp-forming oligonucleotides able to invade into supercoiled DNA via combined Hoogsteen and Watson–Crick binding. To improve the bisLNA design, we investigated its mechanism of binding. Our results suggest that bisLNAs bind via Hoogsteen-arm first, followed by Watson–Crick arm invasion, initiated at the tail. Based on this proposed hybridization mechanism, we designed next-generation bisLNAs with a novel linker able to stack to adjacent nucleobases, a new strategy previously not applied for any type of clamp-constructs. Although the Hoogsteen-arm limits the invasion, upon incorporation of the stacking linker, bisLNA invasion is significantly more efficient than for non-clamp, or nucleotide-linker containing LNA-constructs. Further improvements were obtained by substituting LNA with 2′-glycylamino-LNA, contributing a positive charge. For regular bisLNAs a 14-nt tail significantly enhances invasion. However, when two stacking linkers were incorporated, tail-less bisLNAs were able to efficiently invade. Finally, successful targeting of plasmids inside bacteria clearly demonstrates that strand invasion can take place in a biologically relevant context.

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Section: Discussionmentioning

confidence: 65%

Next-generation bis-locked nucleic acids with stacking linker and 2′-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes

et al. 2016

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“…The averaged conformation of the duplex at 400 K also differs from that at 300 K (RMSD 1ds = 3.92 Å). These effects are caused by unwinding of terminal pairs and/or base flipping from the duplex which were observed experimentally − and studied using MD simulation …”

Section: Resultsmentioning

confidence: 99%

Evaluation of the Gibbs Free Energy Changes and Melting Temperatures of DNA/DNA Duplexes Using Hybridization Enthalpy Calculated by Molecular Dynamics Simulation

2015

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A molecular dynamics simulation approach was applied for the prediction of the thermal stability of oligonucleotide duplexes. It was shown that the enthalpy of the DNA/DNA complex formation could be calculated using this approach. We have studied the influence of various simulation parameters on the secondary structure and the hybridization enthalpy value of Dickerson-Drew dodecamer. The optimal simulation parameters for the most reliable prediction of the enthalpy values were determined. The thermodynamic parameters (enthalpy and entropy changes) of a duplex formation were obtained experimentally for 305 oligonucleotides of various lengths and GC-content. The resulting database was studied with molecular dynamics (MD) simulation using the optimized simulation parameters. Gibbs free energy changes and the melting temperatures were evaluated using the experimental correlation between enthalpy and entropy changes of the duplex formation and the enthalpy values calculated by the MD simulation. The average errors in the predictions of enthalpy, the Gibbs free energy change, and the melting temperature of oligonucleotide complexes were 11%, 10%, and 4.4 °C, respectively. We have shown that the molecular dynamics simulation gives a possibility to calculate the thermal stability of native DNA/DNA complexes a priori with an unexpectedly high accuracy.

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“…Synaptic complex folding requires DNA duplex melting. The formation of right-handed crossovers may trigger such melting and lead to noncanonical secondary structure folding [ 58 , 59 ]. Most right-handed crosses require cytosine-phosphate group interactions at the anchoring point and are frequently stabilised by divalent cations (usually Mg 2+ ).…”

Section: Discussionmentioning

confidence: 99%

Spontaneous DNA Synapsis by Forming Noncanonical Intermolecular Structures

et al. 2022

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We report the spontaneous formation of DNA-DNA junctions in solution in the absence of proteins visualised using atomic force microscopy. The synapsis position fits with potential G-quadruplex (G4) sites. In contrast to the Holliday structure, these conjugates have an affinity for G4 antibodies. Molecular modelling was used to elucidate the possible G4/IM-synaptic complex structures. Our results indicate a new role of the intermolecular noncanonical structures in chromatin architecture and genomic rearrangement.

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DNA-Directed Base Pair Opening

Cited by 6 publications

References 55 publications

Next-generation bis-locked nucleic acids with stacking linker and 2′-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes

Next-generation bis-locked nucleic acids with stacking linker and 2′-glycylamino-LNA show enhanced DNA invasion into supercoiled duplexes

Evaluation of the Gibbs Free Energy Changes and Melting Temperatures of DNA/DNA Duplexes Using Hybridization Enthalpy Calculated by Molecular Dynamics Simulation

Spontaneous DNA Synapsis by Forming Noncanonical Intermolecular Structures

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