A5084793955- DNA Repair Mechanisms
- HIV Research and Treatment
- Cancer-related gene regulation
- Immune Cell Function and Interaction
- CRISPR and Genetic Engineering
- Cancer therapeutics and mechanisms
- Genomics and Chromatin Dynamics
- interferon and immune responses
- RNA modifications and cancer
- T-cell and B-cell Immunology
- Bioactive Compounds and Antitumor Agents
- Toxin Mechanisms and Immunotoxins
- Immunotherapy and Immune Responses
- Microtubule and mitosis dynamics
- NF-κB Signaling Pathways
- Ferroptosis and cancer prognosis
- Bacterial Genetics and Biotechnology
- RNA Interference and Gene Delivery
- Chemokine receptors and signaling
- RNA Research and Splicing
- Signaling Pathways in Disease
- Virus-based gene therapy research
- Herpesvirus Infections and Treatments
- Cytomegalovirus and herpesvirus research
- HIV/AIDS drug development and treatment
Institut de Génétique Humaine
2013-2025
Centre National de la Recherche Scientifique
2013-2025
Université de Montpellier
2007-2025
La Ligue Contre le Cancer
2024
Centre Hospitalier Universitaire de Montpellier
2007
Institut de Génétique Moléculaire de Montpellier
2007
Hôpital Gui de Chauliac
2002-2007
National Institute of Allergy and Infectious Diseases
2007
National Institutes of Health
2007
Institut de Pharmacologie Moléculaire et Cellulaire
2007
MicroRNAs (miRNAs) are single-stranded noncoding RNAs of 19 to 25 nucleotides that function as gene regulators and a host cell defense against both RNA DNA viruses. We provide evidence for physiological role the miRNA-silencing machinery in controlling HIV-1 replication. Type III RNAses Dicer Drosha, responsible miRNA processing, inhibited virus replication peripheral blood mononuclear cells from HIV-1–infected donors latently infected cells. In turn, actively suppressed expression...
Ataxia with oculomotor apraxia 2 (AOA-2) and amyotrophic lateral sclerosis (ALS4) are neurological disorders caused by mutations in the gene encoding for senataxin (SETX), a putative RNA:DNA helicase involved transcription maintenance of genome integrity. Here, using ChIP followed high throughput sequencing (ChIP-seq), we report that is recruited at DNA double-strand breaks (DSBs) when they occur transcriptionally active loci. Genome-wide mapping unveiled hybrids accumulate on DSB-flanking...
Abstract Oncogene-induced replication stress (RS) promotes cancer development but also impedes tumor growth by activating anti-cancer barriers. To determine how cells adapt to RS, we have monitored the expression of different components ATR-CHK1 pathway in primary samples. We show that unlike upstream pathway, checkpoint mediators Claspin and Timeless are overexpressed a coordinated manner. Remarkably, reducing levels HCT116 pretumoral impeded fork progression without affecting signaling....
Abstract Background Morus alba has long been used in traditional Chinese medicine to treat inflammatory diseases; however, the scientific basis for such usage and mechanism of action are not well understood. This study investigated M. on leukocyte migration, one key step inflammation. Methods Gas chromatography-mass spectrometry (GC-MS) cluster analyses supercritical CO 2 extracts three species were performed chemotaxonomy-aided plant authentication. Phytochemistry CXCR4-mediated chemotaxis...
TAR DNA-binding protein 43 (TDP-43; also known as TARDBP) is an RNA-binding whose aggregation a hallmark of the neurodegenerative disorders amyotrophic lateral sclerosis and frontotemporal dementia. TDP-43 loss increases DNA damage compromises cell viability, but actual function in preventing genome instability remains unclear. Here, we show that R-loop formation transcription-dependent manner results replication stress. nucleic-acid-binding self-assembly activities are important inhibiting...
Abstract Oncogene-induced senescence (OIS) arrests cell proliferation in response to replication stress (RS) induced by oncogenes. OIS depends on the DNA damage (DDR), but also cGAS-STING pathway, which detects cytosolic and induces type I interferons (IFNs). Whether how RS IFN responses cooperate promote remains unknown. Here, we show that induction of H-RAS V12 oncogene immortalized human fibroblasts MRE11 nuclease. Indeed, treatment with inhibitor Mirin prevented RS, micronuclei formation...
We have recently reported that the mean number of CCR5 coreceptors at surface CD4 + T cells (CCR5 density) correlates with viral load and disease progression in HIV-1-infected persons. Here, we definitively establish density determines level virus production identify stages HIV-1 replicative cycle modulated by this effect. show, transducing gene into cells, overexpression resulted an overinfectability. sorted HOS-CD4 -CCR5 two subpopulations, HOS high low , former expressing seven times more...
Despite its expression in different cell types, transient receptor potential V2 (TRPV2) is still the most cryptic members of TRPV channel family. 2-Aminoethoxydiphenyl borate (2APB) has been shown to be a common activator TRPV1, TRPV2, and TRPV3, but 2APB-triggered TRPV2 activation remains thoroughly characterized. In this study, we have developed an assay based on lines stably expressing mouse channels intracellular calcium measurements perform pharmacological profiling channel. Phenyl...
Interferons (IFNs) encode a family of secreted proteins that provide the front-line defence against viral infections. It was recently shown ISG20, new 3'-->5' exoribonuclease member DEDD superfamily exonucleases, represents novel antiviral pathway in mechanism IFN action. In this report, it ISG20 expression is rapidly and strongly induced during human immunodeficiency virus type 1 (HIV-1) infection. addition, demonstrated replication kinetics an HIV-1-derived expressing protein...
The development of multidrug-resistant viruses compromises antiretroviral therapy efficacy and limits therapeutic options. Therefore, it is an ongoing task to identify new targets for develop drugs. Here, we show that indole derivative (IDC16) interferes with exonic splicing enhancer activity the SR protein factor SF2/ASF suppresses production key viral proteins, thereby compromising subsequent synthesis full-length HIV-1 pre-mRNA assembly infectious particles. IDC16 inhibits replication...
Replication and transcription are key aspects of DNA metabolism that take place on the same template potentially interfere with each other. Conflicts between these two activities include head-on or co-directional collisions RNA polymerases, which can lead to formation breaks chromosome rearrangements. To avoid deleterious consequences prevent genomic instability, cells have evolved multiple mechanisms preventing replication forks from colliding machinery. Yet, recent reports indicate...
Hidradenitis suppurativa (HS) is a chronic, relapsing, inflammatory skin disease. HS appears to be primary abnormality in the pilosebaceous-apocrine unit. In this work, we characterized hair follicle stem cells (HFSCs) isolated from patients and more precisely outer root sheath (ORSCs). We showed that had an increased number of proliferating progenitor lost quiescent cells. Remarkably, also progression replication forks was altered ORSCs follicles patients, leading activation ATR/CHK1...
Diffuse large B-cell lymphoma (DLBCL) is the most common hematological malignancy. Although more than half of patients with DLBCL achieve long-term remission, majority remaining succumb to disease. As abnormal iron homeostasis implicated in carcinogenesis and progression many tumors, we searched for alterations metabolism that could be exploited develop novel therapeutic strategies. Analysis gene expression profile cohorts established score (IS), a expression-based risk enabling...
Cancer cells display high levels of oncogene-induced replication stress (RS) and rely on DNA damage checkpoint for viability. This feature is exploited by cancer therapies to either increase RS unbearable or inhibit kinases involved in the response. Thus far, treatments that combine these two strategies have shown promise but also severe adverse effects. To identify novel, better-tolerated anticancer combinations, we screened a collection plant extracts found natural compounds from plant,...
Abstract Background In order to better understand why about 15% of people living with Human Immunodeficiency Virus-1 (PWH) on highly active antiretroviral therapy do not restore their CD4 count, we explored the link previously reported between glutamate plasma level and count. Methods We recruited fourty-four adults HIV-1 aviremic under therapy. Their peripheral blood concentrations in GABA were determined by ELISA. Flow cytometry was used detect receptor, reactive oxygen species (ROS)...
The over-expression of RNase H1 enables the progression replication forks under stress and safeguards genome stability. most common interpretation these observations is that removes R-loops, whose formation would hinder fork progression. Here we challenge this model using an innovative strategy to rapidly deliver ready-made Escherichia coli (RnhA) in live cells. We show RnhA enriched vicinity active it rescues different conditions. However, had no impact on R-loops mapped by DRIP or...
Abstract Background: ADAR1 is a double-stranded RNA editing enzyme that prevents autoimmunity against endogenous transcripts by blocking interferon responses triggered cytosolic sensors. has been proposed as therapeutic target in immuno-oncology, but yet, clinically-actionable predictive biomarkers for inhibition sensitivity are lacking. We used functional genomics to uncover and characterize novel, mechanism-based genetic vulnerability of cancer cells which confers inhibition. Methods: A...