A5037374709- DNA and Nucleic Acid Chemistry
- Advanced biosensing and bioanalysis techniques
- RNA and protein synthesis mechanisms
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Telomeres, Telomerase, and Senescence
- RNA Interference and Gene Delivery
- Click Chemistry and Applications
- Genomics and Chromatin Dynamics
- Photochromic and Fluorescence Chemistry
- Synthesis and Biological Evaluation
- Synthesis and Characterization of Heterocyclic Compounds
- Mitochondrial Function and Pathology
- Synthesis and biological activity
- RNA Research and Splicing
- Photosynthetic Processes and Mechanisms
- Synthesis of heterocyclic compounds
- Chemical Synthesis and Analysis
- Plant Molecular Biology Research
- Polyomavirus and related diseases
- Enzyme Production and Characterization
- Trypanosoma species research and implications
- Chemical Reaction Mechanisms
- Algal biology and biofuel production
- Plant Genetic and Mutation Studies
Centre National de la Recherche Scientifique
2000-2024
Sorbonne Université
2000-2024
Structure et Instabilité des Génomes
2014-2024
Inserm
2014-2024
Université Sorbonne Nouvelle
2018-2024
Muséum national d'Histoire naturelle
2018-2024
Délégation Paris 6
2018
Centre de Gestion Scientifique
2008
Institut Jacques Monod
1996-2006
Université Paris Cité
1996-2003
G-quadruplex structures inhibit telomerase activity and must be disrupted for telomere elongation during S phase. It has been suggested that the replication protein A (RPA) could unwind maintain single-stranded DNA in a state amenable to binding of telomeric components. We show here under near-physiological vitro conditions, human RPA is able bind unfold formed from 21mer sequence. Analyses by native gel electrophoresis, cross-linking fluorescence resonance energy transfer indicate formation...
Human telomere biology disorders (TBD)/short syndromes (STS) are heterogeneous caused by inherited loss-of-function mutations in telomere-associated genes. Here, we identify 3 germline heterozygous missense variants the RPA1 gene 4 unrelated probands presenting with short telomeres and varying clinical features of TBD/STS, including bone marrow failure, myelodysplastic syndrome, T- B-cell lymphopenia, pulmonary fibrosis, or skin manifestations. All cluster to DNA-binding domain A protein. is...
Mechanisms of telomere replication remain poorly defined. It has been suggested that G-rich telomeric strand by lagging mechanisms requires, in a stochastic way, the WRN protein. Here we show this requirement is more systematic than previously thought. Our data are compatible with situation which, absence WRN, DNA synthesis at forks uncoupled, thus allowing to continue on C strand, while single G strands accumulate. We also cells which both and POT1 limiting, G- C-rich shorten, suggesting...
DNA and RNA guanine-quadruplexes (G4s) are stabilized by several cations, in particular potassium sodium ions. Generally, stabilizes guanine-quartet assemblies to a larger extent than sodium; this article we report about higher-order G4 structure more stable potassium. Repeats of the GGGTTA telomeric motif fold into contiguous units. Using three independent approaches (thermal denaturation experiments, isothermal molecular-beacon protein-binding assays), show that (GGGTTA)7GGG sequence,...
The replication protein A (RPA) is a single-stranded DNA-binding that plays an essential role in DNA metabolism. RPA able to unfold G-quadruplex (G4) structures formed by telomeric sequences, function important for telomere maintenance. To elucidate the mechanism through which unfolds G4s, we studied its interaction with oligonucleotides adopt G4 structure extended tail on either side of G4. Binding and unfolding was characterized using several biochemical biophysical approaches presence...
Replication Protein A is a single-stranded (ss) DNA-binding protein that highly conserved in eukaryotes and plays essential roles many aspects of nucleic acid metabolism, including replication, recombination, DNA repair telomere maintenance. It heterotrimeric complex consisting three subunits: RPA1, RPA2 RPA3. possesses four domains (DBD), DBD-A, DBD-B DBD-C RPA1 DBD-D RPA2, it binds ssDNA via multistep pathway. Unlike the subunits, no ssDNA-RPA3 interaction has as yet been observed although...
A new dimeric ligand binds telomeric contiguous G4s, displacing the single-stranded DNA binding RPA more efficiently than its monomeric counterpart.
Replication protein A (RPA) is essential for many facets of DNA metabolism. The RPA gene family expanded in Arabidopsis thaliana with five phylogenetically distinct RPA1 subunits (RPA1A-E), two RPA2 (RPA2A and B), RPA3 (RPA3A B). paralogs exhibit partial redundancy functional specialization replication (RPA1B RPA1D), repair (RPA1C RPA1E), meiotic recombination (RPA1A RPA1C). Here, we show that also differentially impact telomere length set point. Loss resets bulk telomeres at a shorter...
Premature telomere shortening or instability is associated with a group of rare and heterogeneous diseases collectively known as biology disorders (TBDs). Here we identified two unrelated individuals clinical manifestations TBDs short telomeres the identical monoallelic variant c.767A>G; Y256C in RPA2 . Although replication protein A2 (RPA2) mutant did not affect ssDNA binding G-quadruplex-unfolding properties RPA, mutation reduced affinity ubiquitin ligase RFWD3 RPA ubiquitination. Using...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTRNA Photolabeling Mechanistic Studies: X-ray Crystal Structure of the Photoproduct Formed between 4-Thiothymidine and Adenosine upon Near UV IrradiationCarole Saintomé, Pascale Clivio, Alain Favre, Jean-Louis Fourrey, Claude RicheView Author Information Institut de Chimie des Substances Naturelles CNRS, 91198 Gif-sur-Yvette Cedex, France Jacques Monod, CNRS-Université Paris VII 2 Place Jussieu, 75251 Cedex O5, Cite this: J. Am. Chem. Soc....
The photo-crosslinking behaviour of oligonucleotide constructs, incorporating photoactive residues 1–5 at a defined position, has been examined in the presence their DNA (14-mer) and RNA (15-mer) complementary targets using two-fold excess; it revealed moderate but promising irreversible binding efficiency, results which could be anticipated by molecular mechanics case 4.
Telomeres are DNA repeated sequences that associate with shelterin proteins and protect the ends of eukaryotic chromosomes. Human telomeres composed 5'TTAGGG repeats a 3' single-stranded tail, called G-overhang, can be specifically bound by protein hPOT1 (human Protection 1). In vitro studies have shown telomeric G-strand fold into stable contiguous G-quadruplexes (G4). present study we investigated how hPOT1, in complex its partner TPP1, binds to structured G4 potassium solutions. We...
Abstract Homologous recombination is a conserved DNA repair process mandatory for chromosome segregation during meiosis. RPA, ubiquitous complex essential to recombination, thought play similar role mitotic and meiotic recombination. MEIOB, meiosis-specific factor with unknown molecular function, ressembles RPA subunit. Here we use in vivo approaches show that mouse spermatocytes, DMC1 RAD51 appear be normally loaded the absence of MEIOB but are prematurely lost from unrepaired sites. This...