2025
Summary
- Study of the interaction between alphasynuclein, a protein implicated in Parkinson’s disease, and plastic particles
- Sinorhizobium meliloti FcrX coordinates cell cycle and division during free-living growth and symbiosis by a ClpXP-dependent mechanism
- The cyanobacterium G. lithophora is a promising organism for effective bioremediation of waters contaminated with 90Sr
- Yin-Yang during DNA replication
- A bifunctional snoRNA guides rRNA 2’-O-methylation and scaffolds gametogenesis effectors
- Borders in our chromosomes shape the neighboring domains
- Ribosome profiling and immunopeptidomics reveal tens of novel conserved HIV-1 ORF encoding T cell antigens
- Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3
- Synthetic mycolates derivatives to decipher protein mycoloylation, a unique post-translational modification in bacteria.
- The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics
- Complete description of the biosynthetic process of [2Fe-2S] clusters
- Genetic differentiation in the MAT-proximal region is not sufficient for suppressing recombination in Podospora anserina
- Regulation of DNA Topology in Archaea: State of the Art and Perspectives
- Epigenetic control of T-DNA during transgenesis and pathogenesis
- It is with deep sadness that we inform you of the passing of Jean-Luc Férat, which occurred on Friday, January 3, 2025.
Study of the interaction between alphasynuclein, a protein implicated in Parkinson’s disease, and plastic particles
Can the presence of microplastics in the brain affect proteins?
Plastics are now part of our daily lives because they are used in so many different ways. They are therefore a major source of pollution. Their chemical stability has consequently become a major concern for the environment and health, given their presence in all ecosystems. The penetration of plastic particles into living organisms through ingestion or inhalation has now been widely demonstrated. Micro- and nanoplastics are found throughout the human body, including in the brain, which raises the question of their potential toxicity. In a biological environment, the plastic particle does not remain naked but interacts with the surrounding molecules to form a biocorona. In this study, Tripathi et al. investigate the binding behavior of human α-synuclein (hαSn) with polyethylene (PE)-based plastics using molecular dynamics simulations and experimental methods. Their simulations show that (a) hαSn folds into a compact conformation to enhance intramolecular interactions, (b) non-oxidised PE nanoplastics facilitate the rapid adsorption of hαSn onto its surface with a change in the structural properties of hαSn, and (c) oxidised nanoplastics fail to capture hαSn. The experimental dynamic light scattering and adsorption isotherms are in good agreement with simulations. The observed formation of the plastic nanoparticle complex with hαSn can be proposed as a plausible pathogenic driving force in neuronal dysfunction and subsequent neurological damage..
More information: https://doi.org/10.1021/acs.biomac.4c00918
Contact: Yves BOULARD <yves.boulard@i2bc.paris-saclay.fr>
Sinorhizobium meliloti FcrX coordinates cell cycle and division during free-living growth and symbiosis by a ClpXP-dependent mechanism
In this study, a new essential player of cell cycle regulation has been characterized in the nitrogen fixing symbiont Sinorhizobium meliloti.
During the nitrogen-fixing symbiosis between the alphaproteobacterium Sinorhizobium meliloti and the plant Medicago sativa (alfalfa), the interplay of molecular mechanisms governing cell cycle and bacteroid differentiation is a remarkable system that has still many details to be discovered. Here, we describe a bacterial cell cycle regulator, named FcrX, that controls two of the main essential players of cell cycle and bacteroid differentiation: the master regulator CtrA and the tubulin-like Z-ring component FtsZ. This essential factor is potentially participating with the degradosome complex driving the proteolysis of those two important regulators. Constitutive expression of FcrX during nodule development shows an increase of plant biomass, opening interesting paths in the amelioration of biological nitrogen fixation for a sustainable agriculture.
More information: https://www.pnas.org/doi/10.1073/pnas.2412367122
Contact: Emanuele BIONDI <emanuele.biondi@i2bc.paris-saclay.fr>
The cyanobacterium G. lithophora is a promising organism for effective bioremediation of waters contaminated with 90Sr
The unicellular cyanobacterium Gloeomargarita lithophora is able to stably sequester and withstand 90Sr and efficiently remove this hazardous anthropogenic radionuclide from aqueous solutions, including a synthetic nuclear effluent.
Strontium (Sr) is an alkaline earth metal commonly occurring in nature. In aqueous environments, it prevails as Sr2+ ions form chemically similar to Ca2+. In most organisms, the non-selective Sr intake primarily comes from water and food. In human, it is mainly localized in bones and dental enamel and is involved in the control of bone formation. Radioactive isotopes such as 90Sr are artificially produced by nuclear fission. 90Sr, a b-emitter with a half-life of 28.8 years, is one of the most hazardous anthropogenic radionuclides. It has been massively released into the environment during nuclear weapons testing and nuclear reactor accidents, such as those at Chernobyl and Fukushima. It is also found in radioactive water effluents produced by nuclear power plants, requiring specific treatment before being discharged. In humans, its accumulation in bone tissues increases the risk of cancers. Current physico-chemical techniques for remediating 90Sr traces from effluents are costly and can exhibit a low selectivity for Sr over Ca. Therefore, there is an incentive to develop an alternative method of remediation. In this study, we demonstrate that the cyanobacterium Gloeomargarita lithophora can remove more than 90% of the 90Sr activity that could be found in a nuclear plant effluent within 24 hours. This process occurs through two steps: a first rapid and passive phase of 90Sr sorbtion to the cell surface, followed by an active phase of 90Sr accumulation within the cells, partially driven by photosynthesis. We also showed that this cyanobacterium is able to stably sequester and withstand 90Sr and to efficiently remove this hazardous radionuclide from aqueous solutions, including a synthetic nuclear effluent. These results highlight Gloeomargarita lithophora as a promising solution for effective bioremediation of water contaminated with 90Sr thereby safeguarding the well-being of our ecosystems.
More information: https://www.sciencedirect.com/science/article/pii/S0304389425010702?via%3Dihub
Contact: Corinne CASSIER CHAUVAT <corinne.cassier-chauvat@i2bc.paris-saclay.fr>
Yin-Yang during DNA replication
DNA duplication of the genetic material is a crucial step of cell proliferation. The study reveals that this step comprises two opposed strategies, coordinated by the enzyme Plk1.
In vertebrates, DNA replication involves the activation of thousands of starting points for DNA copying, known as “origins of replication”. These points are irregularly scattered across the genome. However, the precise mechanisms controlling the coordinated activation of these starting points and the regulation of the rate at which DNA is copied remain poorly understood. Any dysfunction can lead to genetic abnormalities and promote the development of cancers.
The scientists studied DNA replication using cell-free extracts from the eggs of the amphibian Xenopus laevis. This model is quite similar to replication in human cells, and has made it possible to develop a new method for analyzing the distribution of replication starting points (initiations) and the speed of replication in individualized DNA molecules. Combining this analysis with kinetic models, the scientists discovered that DNA replication relies on two dynamic and opposing strategies:
A fast strategy: high replication speed, but with fewer starting points.
A slow strategy: a slower replication speed compensated by the activation of numerous starting points.
In this context, the scientists determined that the enzyme Polo-like kinase 1 (Plk1) played a key role in coordinating these two strategies. Plk1, frequently mutated in many cancers, regulates this balance, opening up new perspectives on the control of replication and its implications in oncology. Published by Paris-Saclay and CNRS Biologie Actu (https://www.insb.cnrs.fr/fr/cnrsinfo/yin-yang-dans-la-duplication-des-chromosomes)
More information: https://academic.oup.com/nar/article/53/3/gkaf007/7990345
Contact: GOLDAR Arach <Arach.GOLDAR@i2bc.paris-saclay.fr>
A bifunctional snoRNA guides rRNA 2’-O-methylation and scaffolds gametogenesis effectors
This study uncovers a fission yeast small nucleolar RNA (snoRNA) that guides ribosomal RNA 2’- O-methylation and modulates the activities of RNA-binding proteins involved in gametogenesis, expanding our vision of the non-canonical functions exerted by snoRNAs.
Small nucleolar RNAs are non-coding transcripts that guide chemical modifications of RNA substrates and modulate gene expression at the epigenetic and post-transcriptional levels. However, the extent of their regulatory potential and the underlying molecular mechanisms remain poorly understood. In a collaborative work with the I2BC B3S department and NGS facility, the epiRNA-Seq facility in Nancy and the Palancade lab at the Institut Jacques Monod, we have identified a conserved, previously unannotated intronic C/D-box snoRNA, termed snR107, hosted in the fission yeast long non-coding RNA mamRNA and carrying two independent cellular functions. On the one hand, snR107 guides site-specific 25S rRNA 2’-O-methylation and promotes pre-rRNA processing and 60S subunit biogenesis. On the other hand, snR107 associates with the gametogenic RNA-binding proteins Mmi1 and Mei2, mediating their reciprocal inhibition and restricting meiotic gene expression during sexual differentiation. Both functions require distinct cis-motifs within snR107, including a conserved 2’-O-methylation guiding sequence. Together, our results position snR107 as a dual regulator of rRNA modification and gametogenesis effectors, expanding our vision on the non-canonical functions exerted by snoRNAs in cell fate decisions.
More information: https://www.nature.com/articles/s41467-025-58664-y
Contact: Mathieu ROUGEMAILLE <mathieu.rougemaille@i2bc.paris-saclay.fr>
Borders in our chromosomes shape the neighboring domains
Researchers at the I2BC and the Ecole Normale Supérieure found that the borders that create separation between functional domains in our chromosomes have an unexpectedly large influence on those domains themselves.
Chromosomes in man and other mammals are subdivided into “functional neighborhoods” that guide the fidelity of biological processes, including gene regulation and DNA repair. Perturbations of these neighborhoods, resulting in the fusion of adjacent domains, can lead to a variety of diseases, including cancer and developmental disorders.
In a study published in PNAS (Proceedings of the National Academy of Sciences of the USA), scientists from the Noordermeer group at the I2BC, together with their colleagues at the Ecole Normale Supérieure in Paris, report how chromosomal border elements influence the organization of the adjacent functional neighborhoods. By combining genomics-based analysis and biophysical simulations of chromosome structure, they find that the size of these borders is highly diverse, from simple “points” on the chromosome to highly extended zones of transition between neighborhoods. Computer simulations of chromosome behavior of different types of borders in-between revealed an unexpected and far-reaching impact of the borders on their neighboring domains. Rather than creating a static separation, the borders will actively influence the degree of neighborhood mixing due to a previously unrecognized mechanism whereby the borders reel-in the adjacent neighborhoods. At narrow borders, this actively promotes mixing and may cause interference between biological activity on both side of the border. Extended borders buffer against this mechanism by adding additional separation. Border structure can thus constitute a new regulatory layer in the genome to fine-tune biological processes.
More information: https://www.pnas.org/doi/10.1073/pnas.2413112122
Contact: Daan NOORDERMEER <daan.noordermeer@i2bc.paris-saclay.fr>
Ribosome profiling and immunopeptidomics reveal tens of novel conserved HIV-1 ORF encoding T cell antigens.
The translatome of HIV-1 reveals tens of alternative open reading frames (ARF), encoding conserved viral antigens. In vivo, ARF-derived peptides elicit potent HIV-specific poly-functional T cell responses mediated by both CD4+ and CD8+ T cells.
T lymphocytes play a pivotal role in controlling human immunodeficiency virus type 1 (HIV-1) infection. Their activation relies on the recognition of viral peptides, or antigens, presented on the surface of infected cells by major histocompatibility complex (MHC) molecules. It is widely assumed that these antigens arise solely from canonical HIV proteins.
Previously, we showed that HIV-specific T lymphocytes can also target peptides derived from HIV alternative reading frames (ARFs) presented by MHC molecules. However, evidence for ARFs in the HIV genome had thus far been indirect. In this new study, using ribosome profiling (RiboSeq), we identified the complete HIV-1 translatome in infected CD4⁺ T cells. This approach systematically identified virally encoded mRNA sequences actively translated in HIV-infected cells. We found that the HIV-1 genome contains over one hundred ARFs located either in the 5ʹ untranslated region (5ʹUTR) of classical viral genes or overlapping canonical HIV open reading frames.
Using two complementary methods: (1) detecting T lymphocytes specific to ARF-derived peptides in PBMCs from people living with HIV and (2) directly isolating ARF-derived peptides bound to MHC molecules via mass spectrometry–based immunopeptidomics—we demonstrate that HIV ARFs encode novel viral antigens capable of eliciting broad and potent T-cell responses. Our results expand the range of HIV antigens that could be harnessed for vaccine development and may also reveal the existence of microproteins or pseudogenes in the HIV genome.
These findings stem from the work of two complementary teams at I2BC: one led by Olivier Namy, a specialist in protein translation, and the other led by Arnaud Moris, an expert in the immune response to HIV. This collaboration also involved French research and clinical teams and the University of Tübingen in Germany.
More information: https://doi.org/10.1038/s41467-025-56773-2
Contact: Olivier NAMY <olivier.namy@i2bc.paris-saclay.fr> & Arnaud MORIS <arnaud.moris@i2bc.paris-saclay.fr>
Alternative silencing states of transposable elements in Arabidopsis associated with H3K27me3
This study sheds light on an alternative mode of Transposable Element silencing associated with H3K27me3 instead of DNA methylation in flowering plants; it also indicates dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes.
Background
The DNA/H3K9 methylation and Polycomb-group proteins (PcG)-H3K27me3 silencing pathways have long been considered mutually exclusive and specific to transposable elements (TEs) and genes, respectively in mammals, plants, and fungi. However, H3K27me3 can be recruited to many TEs in the absence of DNA/H3K9 methylation machinery and sometimes also co-occur with DNA methylation.
Results
In this study, we show that TEs can also be solely targeted and silenced by H3K27me3 in wild-type Arabidopsis plants. These H3K27me3-marked TEs not only comprise degenerate relics but also seemingly intact copies that display the epigenetic features of responsive PcG target genes as well as an active H3K27me3 regulation. We also show that H3K27me3 can be deposited on newly inserted transgenic TE sequences in a TE-specific manner indicating that silencing is determined in cis. Finally, a comparison of Arabidopsis natural accessions reveals the existence of a category of TEs—which we refer to as “bifrons”—that are marked by DNA methylation or H3K27me3 depending on the accession. This variation can be linked to intrinsic TE features and to trans-acting factors and reveals a change in epigenetic status across the TE lifespan.
Conclusions
Our study sheds light on an alternative mode of TE silencing associated with H3K27me3 instead of DNA methylation in flowering plants. It also suggests dynamic switching between the two epigenetic marks at the species level, a new paradigm that might extend to other multicellular eukaryotes..
More information: https://genomebiology.biomedcentral.com/articles/10.1186/s13059-024-03466-6
Contact: Angélique DELERIS <angelique.deleris@i2bc.paris-saclay.fr>
Synthetic mycolates derivatives to decipher protein mycoloylation, a unique post-translational modification in bacteria.
In vitro reconstitution of bacterial protein mycoloylation.
Protein mycoloylation is a newly characterized post-translational modification (PTM) specifically found in Corynebacteriales, an order of bacteria that includes numerous human pathogens. Their envelope is composed of a unique outer membrane, the so-called mycomembrane made of very-long chain fatty acids, named mycolic acids. Recently, some mycomembrane proteins including PorA have been unambiguously shown to be covalently modified with mycolic acids in the model organism Corynebacterium glutamicum by a mechanism that relies on the mycoloyltransferase MytC. This PTM represents the first example of protein O-acylation in prokaryotes and the first example of protein modification by mycolic acid. Through the design and synthesis of trehalose monomycolate (TMM) analogs, we prove that i) MytC is the mycoloyltransferase directly involved in this PTM, ii) TMM, but not trehalose dimycolate (TDM), is a suitable mycolate donor for PorA mycoloylation, iii) MytC is able to discriminate between an acyl and a mycoloyl chain in vitro unlike other trehalose mycoloyltransferases. We also solved the structure of MytC acyl-enzyme obtained with a soluble short TMM analogs which constitutes the first mycoloyltransferase structure with a covalently linked to an authentic mycolic acid moiety. These data highlight the great conformational flexibility of the active site of MytC during the reaction cycle and pave the way for a better understanding of the catalytic mechanism of all members of the mycoloyltransferase family including the essential Antigen85 enzymes in Mycobacteria.
More information: https://doi.org/10.1016/j.jbc.2025.108243
Contact: Florence CONSTANTINESCO-BECKER <florence.constantinesco@i2bc.paris-saclay.fr>
The Asgard archaeal origins of Arf family GTPases involved in eukaryotic organelle dynamics
How did the endomembrane system, unique to eukaryotes, emerge from their prokaryotic ancestors? We report that Arf proteins, which are crucial regulators of membrane dynamics in eukaryotes, originated in the archaeal ancestor of eukaryotes, the Asgard Archaea.
The evolution of eukaryotes is a fundamental event in the history of life. The closest prokaryotic lineage to eukaryotes, the Asgardarchaeota, encode proteins previously found only in eukaryotes, providing insight into their archaeal ancestor. Eukaryotic cells are characterized by endomembrane organelles, and the Arf family GTPases regulate organelle dynamics by recruiting effector proteins to membranes upon activation. The Arf familyis ubiquitous among eukaryotes, but its origins remain elusive. Here we report a group of prokaryotic GTPases, the ArfRs, which are widely present in Asgardarchaeota. Phylogenetic analyses reveal that eukaryotic Arf family proteins arose from the ArfR group. Expression of representative Asgardarchaeota ArfR proteins in yeast and Xray crystallographic studies show that ArfR GTPases possess the mechanism of membrane binding and structural features unique to Arf family proteins. Our results indicate that Arf family GTPases originated in the archaeal ancestor of eukaryotes, consistent with aspects of the endomembrane system evolving early in eukaryogenesis.
More information: https://www.nature.com/articles/s41564-024-01904-6#Abs1
Contact : Julie MENETREY <julie.menetrey@i2bc.paris-saclay.fr>
Complete description of the biosynthetic process of [2Fe-2S] clusters
Iron-sulfur clusters are essential metallocofactors providing catalytic activities to a multitude of enzymes and proteins. Here, we report a comprehensive picture of their assembly mechanism, showing that it relies on the formation of [1Fe-1S] precursors fused into [2Fe-2S] clusters upon dimerization of the scaffold protein.
Iron-sulfur (Fe-S) clusters are ubiquitous metallocofactors constituting the active site of a multitude of enzymes and proteins involved in electron transfer, catalysis, sulfur donation and signalling. They are made of iron and sulfide ions assembled into diverse structures. The [2Fe-2S] and [4Fe-4S] clusters are the most common forms in organisms. They are synthesized by multi-protein machineries which have remained highly conserved during evolution. The iron-sulfur cluster (ISC) assembly machinery present in eukaryotes and prokaryotes synthesizes [2Fe-2S] clusters, which serve as building blocks for the assembly of [4Fe-4S] clusters. The core ISC machinery assembles [2Fe-2S] clusters on the scaffold protein IscU, which requires iron provided by an unknown source, sulfur provided in the form of cysteine bound persulfides (Cys-SSH) by the cysteine desulfurase IscS, and electrons provided by the ferredoxin–ferredoxin reductase complex Fdx-FdxR from NADPH. Then, specialized chaperones transfer [2Fe-2S] clusters to recipient acceptors. Despite previous studies on the core assembly machinery, the mechanistic details of the [2Fe-2S] cluster assembly process have remained poorly understood due to the experimental difficulties in trapping the relevant intermediates.
The team Biochemistry of Metalloproteins and Associated Diseases at the Institute of Integrative Biology of the Cell in Gif-Sur-Yvette (I2BC, UMR 9198, CNRS – CEA – Paris-Saclay University) managed to dissect this process step by step and to isolate several key intermediates using a functional reconstitution of the Escherichia coli ISC machinery. They used a combination of biochemical techniques to trap these intermediates: anaerobic reconstitution, persulfide detection assays, kinetics, UV-visible, circular dichroism, and to characterize them by spectroscopic methods: electron paramagnetic spectroscopy (EPR), nuclear magnetic resonance (NMR) and native mass spectrometry (nMS) in collaboration with teams at Aix-Marseille University (BIP), Gif-Sur-Yvette (ICSN) and Strasbourg (IPHC). They show that the assembly of [2Fe-2S] clusters is initiated by iron binding to IscU, which triggers persulfide insertion by IscS in the vicinity of the iron-binding site of IscU upon the formation of a complex between IscU and IscS. The persulfide in IscU binds to the iron center and is cleaved into sulfide by the Fdx-FdxR complex, which leads to the formation of a Fe-SH intermediate, referred to as the [1Fe-1S] precursor. Then, IscU dissociates from IscS, dimerizes and generates a bridging [2Fe-2S] cluster by fusion of two [1Fe-1S] precursors. The IscU dimer ultimately dissociates into a monomer, ready to transfer its [2Fe-2S] cluster to acceptors. The data also indicate that the bridging cluster is initially in the super-reduced state [2Fe-2S]0 and releases two electrons to the ferredoxin enzyme, thereby leading to an oxidised [2Fe-2S]2+ state as the final product.
These data provide a comprehensive description of mechanism of [2Fe-2S] clusters assembly by the bacterial ISC machinery, highlighting the formation of key intermediates through a tightly concerted process. This stepwise dissection further supports findings in eukaryotes, including iron loading, persulfidation and dimerization of IscU, which point to an evolutionary conservation of the assembly process.
More information: https://www.nature.com/articles/s41589-024-01818-8
Contact : Benoit D’AUTRÉAUX <benoit.dautreaux@i2bc.paris-saclay.fr>
Genetic differentiation in the MAT-proximal region is not sufficient for suppressing recombination in Podospora anserina
A large genomic region in Podospora anserina remains entirely devoid of crossovers, despite being fully colinear.
Recombination is advantageous over the long-term, as it allows efficient selection and purging deleterious mutations. Nevertheless, recombination suppression has repeatedly evolved in sex chromosomes. In fungi, sexual compatibility is driven by a locus called mating-type (mat), around which recombination suppression is also often observed.
The evolutionary causes for recombination suppression and the proximal mechanisms preventing crossing overs are poorly understood. Several hypotheses have recently been suggested based on theoretical models, and in particular, that divergence could accumulate neutrally around a sex-determining region and reduce recombination rates, a self-reinforcing process that could foster progressive extension of recombination suppression.
We used the ascomycete fungus Podospora anserina for investigating these questions: a 0.8 Mbp region around its mat locus is non-recombining (called MAT-proximal region), despite being collinear between the two mating types. This fungus is mostly selfing, resulting in highly homozygous individuals, except in the non-recombining region around the mating-type locus that displays differentiation between mating types. Here, we test the hypothesis that sequence divergence alone is responsible for recombination cessation. We replaced one mat idiomorph by the sequence of the other, to obtain compatible strains isogenic in the MAT-proximal region. Crosses showed that recombination was still suppressed in that context, indicating that other proximal mechanisms than inversions or mere sequence divergence are responsible for recombination suppression in this fungus.
This finding suggests that selective mechanisms likely acted for suppressing recombination, or the spread of epigenetic marks, as the neutral model based on mere nucleotide divergence does not seem to hold in P. anserina.
More information: https://academic.oup.com/g3journal/advance-article/doi/10.1093/g3journal/jkaf015/7978232
Contact : Pierre GROGNET <pierre.grognet@i2bc.paris-saclay.fr>
It is with deep sadness that we inform you of the passing of Jean-Luc Férat, which occurred on Friday, January 3, 2025.
It was with great sadness that we learned of the death of our colleague Jean-Luc Ferat on January 3, at the age of 59, after a 10-year fight against cancer. During these years, Jean-Luc showed extraordinary courage in continuing his teaching and research.
Recruited by the University of Versailles Saint-Quentin-en-Yvelines in 1997, Jean-Luc Ferat was appointed Professor of Molecular Biology and Genetics at the UFR Sciences du Vivant of the Université Paris Cité in September 2022. Throughout his career, he has pursued his research and teaching activities with passion and determination.
Jean-Luc’s research in bacterial biology and molecular genetics has always included a phylogenetic and bioinformatics component, which he has never abandoned and which makes his work so original. During his thesis at the CGM in Gif/Yvette, under the supervision of François Michel, he discovered the presence of group II introns in bacteria, at the origin of the eukaryotic RNA splicing machinery. He then worked with Nancy Kleckner at Harvard University on the coordination between replication initiation and the cell cycle in Escherichia coli.
Back in France at the CGM in 2001, Jean-Luc developed an original approach to comparing organisms based on the presence of protein domains. This enabled him to propose the existence of links between genes involved in DNA maintenance and the methylation machinery of certain bacteria, links that were confirmed experimentally by other teams. Using the same approach, Jean-Luc identified the ancestral protein responsible for bacterial replicative helicase activity at initiation, DciA, and experimentally confirmed his discovery. Then, as part of François-Xavier Barre’s team at I2BC, he showed that DciA ensures bidirectionality of replication initiation and that unidirectional initiation leads to a topological catastrophe, suggesting why initiation is bidirectional in all 3 domains of life. This is the work he has been developing since joining Marie-Noëlle Prioleau’s team at the Institut Jacques Monod.
Jean-Luc applied the same high standards to his teaching as to his research. At the Université de Versailles Saint-Quentin-en-Yvelines, Jean-Luc taught in all years of training. In particular, he was in charge of the first-year students in Biochemistry and Molecular Biology for about ten years. He has initiated or participated in the creation of a large number of courses from L1 to M2. In particular, he has been a driving force behind the creation of courses combining molecular biology, genomics, genetics, bioinformatics and phylogeny.
Thanks to this multidisciplinary approach, he played a key role in the creation of the first master’s degree in “Bioinformatics and Genomics”. As part of the merger of the Master’s programs of the 3 sites UEVE, UVSQ and the Faculty of Science Orsay under the banner of the Université Paris-Saclay, he was also behind the creation and inauguration in 2015 of an original Master’s program entitled “Biodiversity, Genomics and the Environment”. To achieve this, he was able to convince and involve members of AgroParisTech and INRAE. He was in charge of this program until 2022 when he was recruited by the Université Paris Cité. After his new appointment as university professor, Jean-Luc immediately became involved in the teaching teams, sharing his experience and scientific vision and contributing to the development of certain courses. He was also a driving force behind the revision of the L3 molecular biology courses and the changes to the BMC Masters curriculum, making a significant contribution to the improvement of the curricula.
Jean-Luc was passionate about his work and eager to share his scientific enthusiasm. He cared about the future of his students and guided them with a rigor that pushed them to be the best they could be. His vast scientific knowledge led to discussions that were often passionate and fascinating. We will also remember him for his general knowledge, his concern for the common good, and his freedom of thought.
Finally, for almost 10 years, Jean-Luc faced his illness with great clarity, strength of character and admirable courage. He spent his last moments caring for his daughter, his family, his students and his colleagues.
Our thoughts are with his daughter and his family, to whom we offer our full support and our sincerest condolences.
Regulation of DNA Topology in Archaea:
State of the Art and Perspectives
How do Archaea manage entangled DNA in their cells? This review summarizes current knowledge of the molecular mechanisms involved, with a focus on topoisomerases, and explores future research directions to address this fundamental question.
DNA topology is a direct consequence of the double helical nature of DNA and is defined by how the two complementary DNA strands are intertwined. Virtually every reaction involving DNA is influenced by DNA topology or has topological effects. It is therefore of fundamental importance to understand how this phenomenon is controlled in living cells. DNA topoisomerases are the key actors dedicated to the regulation of DNA topology in cells from all domains of life. While significant progress has been made in the last two decades in understanding how these enzymes operate in vivo in Bacteria and Eukaryotes, studies in Archaea have been lagging behind. This review article aims to summarize what is currently known about DNA topology regulation by DNA topoisomerases in main archaeal model organisms. These model archaea exhibit markedly different lifestyles, genome organization and topoisomerase content, thus highlighting the diversity and the complexity of DNA topology regulation mechanisms and their evolution in this domain of life. The recent development of functional genomic assays supported by next-generation sequencing now allows to delve deeper into this timely and exciting, yet still understudied topic.
More information: http://doi.org/10.1111/mmi.15328
Contact : Tamara BASTA <tamara.basta@i2bc.paris-saclay.fr>
Epigenetic control of T-DNA during transgenesis and pathogenesis
T-DNAs are mobile elements transferred from pathogenic Agrobacterium to plants that reprogram host cells into hairy roots or tumors, and which are used as disarmed forms to deliver transgenes in plants. Here we review the mechanisms that silence the expression of T-DNAs in transgenic plants as well as during pathogenesis.
Mobile elements known as T-DNAs are transferred from pathogenic Agrobacterium to plants and reprogram the host cell to form hairy roots or tumors. Disarmed nononcogenic T-DNAs are extensively used to deliver transgenes in plant genetic engineering. Such T-DNAs were the first known targets of RNA silencing mechanisms, which detect foreign RNA in plant cells and produce small RNAs that induce transcript degradation. These T-DNAs can also be transcriptionally silenced by the deposition of epigenetic marks such as DNA methylation and the dimethylation of lysine 9 (H3K9me2) in plants. Here, we review the targeting and the roles of RNA silencing and DNA methylation on T-DNAs in transgenic plants as well as during pathogenesis. In addition, we discuss the crosstalk between T-DNAs and genome-wide changes in DNA methylation during pathogenesis. We also cover recently discovered regulatory phenomena, such as T-DNA suppression and RNA silencing-independent and epigenetic-independent mechanisms that can silence T-DNAs. Finally, we discuss the implications of findings on T-DNA silencing for the improvement of plant genetic engineering.
More information: https://academic-oup-com.insb.bib.cnrs.fr/plphys/advance-article/doi/10.1093/plphys/kiae583/7876130
Contact : Angélique DELERIS <angelique.deleris@i2bc.paris-saclay.fr>