- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- Bacteriophages and microbial interactions
- Molecular Junctions and Nanostructures
- Plant Virus Research Studies
- Telomeres, Telomerase, and Senescence
- Muon and positron interactions and applications
- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Advanced NMR Techniques and Applications
- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Click Chemistry and Applications
- CRISPR and Genetic Engineering
- HIV/AIDS drug development and treatment
- RNA Research and Splicing
- Research on Leishmaniasis Studies
- Trypanosoma species research and implications
- Metal complexes synthesis and properties
- Chromosomal and Genetic Variations
- Microfluidic and Capillary Electrophoresis Applications
- Nanoplatforms for cancer theranostics
- Cancer therapeutics and mechanisms
Czech Academy of Sciences, Institute of Biophysics
2017-2025
Nanjing University
2018-2025
Inserm
2016-2025
École Polytechnique
1996-2025
Centre National de la Recherche Scientifique
2016-2025
Université Paris-Saclay
2019-2024
Czech Academy of Sciences
2017-2024
Institut Européen de Chimie et Biologie
2014-2023
Université de Bordeaux
2014-2023
Régulations Naturelle et Artificielle
2012-2023
Oligodeoxynucleotides which include stretches of guanines form a well-known tetrameric structure. We show that the recording reversible absorbance changes at 295 nm allows to precisely monitor intramolecular guanine (G)-quartet formation and dissociation. Accurate Tm thermodynamic values could be easily extracted from data, whereas classical recordings 260 led much larger uncertainty in extreme cases, completely inaccurate measurements. This inverted denaturation profile was observed for all...
Critical evidence for the biological relevance of Gquadruplexes (G4) has recently been obtained in seminal studies performed a variety organisms.Four-stranded G-quadruplex DNA structures are promising drug targets as these non-canonical appear to be involved number key processes.Given growing interest G4, accurate tools predict propensity given or RNA sequence needed.Several algorithms such Quadparser quadruplex forming propensity.However, have established that sequences not detected by do...
Syntheses and telomeric G-quadruplex−DNA binding properties of novel bisquinolinium compounds are reported. This series exhibits remarkable efficiency both in terms stabilization selectivity, thus combining the performances most potent quadruplex binders reported so far. These then represent an ideal tradeoff between rapid synthetic access efficient target recognition. The study also highlights important structural parameters that lead to design highly selective G-quadruplex binders.
We show that nucleic acid structures may be conveniently and inexpensively characterized by their UV thermal difference spectra. A spectrum (TDS) is obtained for a simply recording the ultraviolet absorbance spectra of unfolded folded states at temperatures above below its melting temperature ( Tm ). The between these two TDS. TDS has specific shape unique each type structure, conclusion based on comparison >900 from 200 different sequences. reflects subtleties base stacking interactions...
We compared here 80 different sequences containing four tracts of three guanines with loops variable length (between 1 and 15 bases for unmodified sequences, up to 30 fluorescently labeled oligonucleotides). All were capable forming stable quadruplexes, T(m) above physiological temperature in most cases. Unsurprisingly, the melting was systematically lower sodium than potassium but difference between both ionic conditions varied >39°C (average difference: 18.3°C). Depending on sequence...
There is currently great interest in the design of nanodevices that are capable performing linear or rotary movements. Protein molecular machines abundant biology but it has recently been proposed nucleic acids could also act as nanomolecular model systems. Several types movements have described with DNA machines: rotation and “scissors-like” opening closing. Here we show a nanomachine an extension–contraction movement. The simple robust device here composed single 21-base oligonucleotide...
Telomeres of human chromosomes contain a G-rich 3′-overhang that adopts an intramolecular G-quadruplex structure in vitro which blocks the catalytic reaction telomerase. Agents stabilize G-quadruplexes have potential to interfere with telomere replication by blocking elongation step catalyzed telomerase and can therefore act as antitumor agents. We identified Fluorescence Resonance Energy Transfer new series quinoline-based ligands also exhibit potent specific anti-telomerase activity IC 50...
In budding yeast, the Pif1 DNA helicase is involved in maintenance of both nuclear and mitochondrial genomes, but its role these processes still poorly understood. Here, we provide evidence for a new function by demonstrating that absence promotes genetic instability alleles G-rich human minisatellite CEB1 inserted Saccharomyces cerevisiae genome, not other tandem repeats. Inactivation helicases, including Sgs1, had no effect on stability. vitro, show repeats formed stable G-quadruplex (G4)...
Thioflavin T (ThT) becomes fluorescent in the presence of G-quadruplex structure such as that formed by human telomeric motif. In this report, we extend and generalize these observations show dye may be used a convenient specific quadruplex probe. most, but not all, G4-forming sequences, observed large increase ThT fluorescence emission, whereas control duplexes single strands had more limited effect on emission. This differential behavior allowed us to design high-throughput assay detect G4...
Abstract C‐rich DNA has the capacity to form a tetra‐stranded structure known as an i‐motif. The i‐motifs within genomic have been proposed contribute regulation of transcription. However, direct experimental evidence for existence these structures in vivo missing. Whether i‐motif complex environment living cells is not currently known. Herein, using state‐of‐the‐art in‐cell NMR spectroscopy, we evaluate stabilities cellular environment. We show that formed from naturally occurring sequences...
Abstract Motivation Expanding research highlights the importance of guanine quadruplex structures. Therefore, easy-accessible tools for analyses in DNA and RNA molecules are important scientific community. Results We developed a web version G4Hunter application. This new web-based server is platform-independent user-friendly application analyses. It allows retrieval gene/nucleotide sequence entries from NCBI databases provides complete characterization localization propensity...
Abstract Genome-wide studies of DNA replication origins revealed that preferentially associate with an Origin G-rich Repeated Element (OGRE), potentially forming G-quadruplexes (G4). Here, we functionally address their requirements for initiation in a series independent approaches. Deletion the OGRE/G4 sequence strongly decreased corresponding origin activity. Conversely, insertion element created new origin. This also promoted episomal EBV vectors lacking viral origin, but not if was...
Guanine-rich sequences can form G-quadruplexes (G4) in living cells, making these structures promising anti-cancer targets. Compounds able to recognize have been investigated as potential anticancer drugs; however, no G4 binder has yet approved the clinic. Here, we describe ligands structure-activity relationships, vivo effects well clinical trials. Addressing ligand characteristics, targeting challenges and this review provides insights into development of potent selective G4-targeting...
Abstract I-Motifs (iM) are non-canonical DNA structures potentially forming in the accessible, single-stranded, cytosine-rich genomic regions with regulatory roles. Chromatin, protein interactions, and intracellular properties seem to govern iM formation at sites i-motif propensity (iMFPS) human cells, yet their specific contributions remain unclear. Using in-cell NMR oligonucleotide iMFPS models, we monitor iM-associated structural equilibria asynchronous cell cycle-synchronized HeLa cells...
The melting of tetramolecular DNA or RNA quadruplexes is kinetically irreversible. However, rather than being a hindrance, this kinetic inertia allows us to study association and dissociation processes independently. From point view, the reaction fourth order in monomer first quadruplex. rate constant kon , expressed M −3 ·s −1 decreases with increasing temperature, reflecting negative activation energy ( Eon ) for sequences presented here. Association favored by an increase monocation...
The reactivation of telomerase activity in most cancer cells supports the concept that is a relevant target oncology, and inhibitors have been proposed as new potential anticancer agents. telomeric G-rich single-stranded DNA can adopt vitro an intramolecular quadruplex structure, which has shown to inhibit activity. We used fluorescence assay identify molecules stabilize G-quadruplexes. Intramolecular folding oligonucleotide with four repeats human sequence into G-quadruplex structure led...
A triple helix is formed upon binding of an oligodeoxynucleotide to the major groove duplex DNA. benzo[e]pyridoindole derivative (BePI) strongly stabilized this structure and showed preferential a triplex rather than duplex. Energy transfer experiments suggest that BePI intercalates within helix. Sequence-specific inhibition transcription initiation specific gene by Escherichia coli RNA polymerase triplex-forming enhanced when BePI. Upon irradiation with ultraviolet light, induces covalent...