A5050656020- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA Interference and Gene Delivery
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Bacteriophages and microbial interactions
- Social Sciences and Governance
- Telomeres, Telomerase, and Senescence
- Bacterial Genetics and Biotechnology
- Molecular Biology Techniques and Applications
- RNA modifications and cancer
- Epigenetics and DNA Methylation
- Multiculturalism, Politics, Migration, Gender
- RNA Research and Splicing
- International Relations in Latin America
- Genomics and Phylogenetic Studies
- Click Chemistry and Applications
- Molecular Junctions and Nanostructures
- Single-cell and spatial transcriptomics
- Indigenous Cultures and History
- Cancer-related gene regulation
- Microfluidic and Capillary Electrophoresis Applications
- Nanopore and Nanochannel Transport Studies
Institut de Biologie de l'École Normale Supérieure
2018-2025
École Normale Supérieure - PSL
2006-2025
Inserm
2007-2023
Centre National de la Recherche Scientifique
2010-2023
Université Paris Sciences et Lettres
2020-2022
Centre de Recherche des Cordeliers
2022
University of Cambridge
2019-2020
Sun Yat-sen University
2020
Laboratoire de Biologie Moléculaire des Eucaryotes
2014-2019
Université Toulouse III - Paul Sabatier
2014-2019
We present the intramolecular G-quadruplex structure of human telomeric DNA in physiologically relevant K(+) solution. This G-quadruplex, whose (3 + 1) topology differs from folds reported previously Na(+) solution and a K(+)-containing crystal, involves following: one anti.syn.syn.syn two syn.anti.anti.anti G-tetrads; double-chain reversal edgewise loops; three G-tracts oriented direction fourth opposite direction. The topological characteristics this scaffold should provide unique platform...
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...
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...
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...
Quadruplex ligands are often considered as telomerase inhibitors. Given the fact that some of these molecules present in clinical setting, it is important to establish validity this assertion. To analyze effects compounds, we used a direct assay with telomerase-enriched extracts. The comparison potent from various chemical families revealed differences terms on initiation and processivity. Although most quadruplex may lock quadruplex-prone sequence into structure inhibits elongation by...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTIntramolecular Folding of Pyrimidine Oligodeoxynucleotides into an i-DNA MotifJean-Louis Mergny, Laurent Lacroix, Xiaogang Han, Jean-Louis Leroy, and Claude HeleneCite this: J. Am. Chem. Soc. 1995, 117, 35, 8887–8898Publication Date (Print):September 1, 1995Publication History Published online1 May 2002Published inissue 1 September 1995https://pubs.acs.org/doi/10.1021/ja00140a001https://doi.org/10.1021/ja00140a001research-articleACS...
A systematic study of the thermal and conformational properties chemically modified G-quadruplexes different molecularities is reported. The effect backbone charge atom size, thymine/uracyl substitution as well modification at ribose 2′-position was analyzed by UV spectroscopy. Additional calorimetric studies were performed on forms human telomeric sequence. Determination differential spectra allowed more insights into oligonucleotides. Lack negative phosphate yielded to a general...
Parallel tetramolecular quadruplexes may be formed with short oligodeoxynucleotides bearing a block of three or more guanines. We analyze the properties sequence variants parallel in which each guanine central was systematically substituted different base. Twelve types substitutions were assessed than 100 sequences. conducted comparative kinetic analysis all tetramers. Electrospray mass spectrometry used to count number inner cations, is an indicator effective tetrads. In general, presence...
The catalytic subunit of human telomerase, hTERT, actively elongates the 3′ end telomere in most cancer cells. hTERT promoter, which contains many guanine-rich stretches on same DNA strand, exhibits an exceptional potential for G-quadruplex formation. Here we show that one particular G-rich sequence this region coexists two conformations potassium solution: a (3 + 1) and parallel-stranded G-quadruplexes. We present NMR solution structures both conformations, each comprising several robust...
Short contiguous arrays of variant CTAGGG repeats in the human telomere are unstable male germline and somatic cells, suggesting formation unusual structures by this repeat type. Here, we report on structure an intramolecular G-quadruplex formed DNA sequences containing four telomeric potassium solution. Our results reveal a new robust antiparallel fold involving two G-tetrads sandwiched between G.C base pair G.C.G.C tetrad, which could represent platform for drug design targeted to DNA.
Abstract Recent studies indicate that i‐DNA, a four‐stranded cytosine‐rich DNA also known as the i‐motif, is actually formed in vivo; however, systematic study on sequence effects stability has been missing. Herein, an unprecedented number of different sequences (271) bearing four runs 3–6 cytosines with spacer lengths tested. While i‐DNA nearly independent total length, central plays special role stability. Stability depends length C‐tracts at both acidic and neutral pHs. This provides...
DNA is an attractive component for molecular recognition, because of its self-assembly properties. Its three-dimensional structure can differ markedly from the classical double helix. For example, or RNA strands carrying guanine cytosine stretches associate into four-stranded structures called G-quadruplexes i-DNA, respectively. Since 2002, several groups have described nanomachines that take advantage this structural polymorphism. We first introduce unusual are involved in these devices...
Control by copper: CuII ions modulate the quadruplex affinity of high-affinity ligand 360A and denaturate folded form DNA 22AG to an unfolded form. So removal copper through complexation enables cycling both unfolding. Since seminal report in 1997 on small molecules designed interact with G-quadruplex DNA,1 impressive number candidates have been evaluated for binding this particular structure.2 The ligands are structurally diverse, combining flat aromatic cores that π-stack external tetrads...
Abstract Genome replication mapping methods profile cell populations, masking cell-to-cell heterogeneity. Here, we describe FORK-seq, a nanopore sequencing method to map of single DNA molecules at 200-nucleotide resolution. By quantifying BrdU incorporation along pulse-chased intermediates from Saccharomyces cerevisiae , orient 58,651 tracks reproducing population-based directionality profiles and 4964 4485 individual initiation termination events, respectively. Although most events cluster...
Abstract Little is known about replication fork velocity variations along eukaryotic genomes, since reference techniques to determine speed either provide no sequence information or suffer from low throughput. Here we present NanoForkSpeed, a nanopore sequencing-based method map and extract the of individual forks detected as tracks thymidine analogue bromodeoxyuridine incorporated during brief pulse-labelling asynchronously growing cells. NanoForkSpeed retrieves previous Saccharomyces...
The telomeric G-rich single-stranded DNA can adopt in vitro an intramolecular quadruplex structure, which has been shown to directly inhibit telomerase activity. reactivation of this enzyme immortalized and most cancer cells suggests that is a relevant target oncology, inhibitors have proposed as new potential anticancer agents. In paper, we analyzed the selectivity four ethidium derivatives itself toward different G-quadruplex species, with electrospray mass spectrometry competitive...
Most studies on the structure of DNA in telomeres have been dedicated to double-stranded region or guanosine-rich strand and consequently little is known about factors that may bind telomere cytosine-rich (C-rich) strand. This led us investigate whether proteins exist can recognise C-rich sequences. We isolated several nuclear from human cell extracts specifically vertebrate [namely a d(CCCTAA)(n)repeat] with high affinity telomeric 100xreduced affinity. A biochemical assay allowed...