A5039696761- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- Chromosomal and Genetic Variations
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Genetics, Aging, and Longevity in Model Organisms
- Advanced biosensing and bioanalysis techniques
- Genetic factors in colorectal cancer
- Cancer-related Molecular Pathways
- Water Quality and Pollution Assessment
- Cancer Diagnosis and Treatment
- Cytomegalovirus and herpesvirus research
- DNA and Nucleic Acid Chemistry
- Water Quality Monitoring and Analysis
- Herpesvirus Infections and Treatments
- RNA Interference and Gene Delivery
- Pharmaceutical and Antibiotic Environmental Impacts
- Viral-associated cancers and disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Immune Cell Function and Interaction
Institut de Recherche sur le Cancer et le Vieillissement de Nice
2018-2023
Institut de Chimie de Nice
2023
Ruijin Hospital
2018-2023
Shanghai Jiao Tong University
2020-2022
Inserm
2013-2022
Université Côte d'Azur
2018-2022
Centre National de la Recherche Scientifique
2013-2022
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
2022
Observatoire de la Côte d’Azur
2021
State Key Laboratory of Medical Genomics
2020
Linear chromosomes are stabilized by telomeres, but the presence of short dysfunctional telomeres triggers cellular senescence in human somatic tissues, thus contributing to ageing. Approximately 1% population inherits a chromosomally integrated copy herpesvirus 6 (CI-HHV-6), consequences integration for virus and telomere with insertion unknown. Here we show that on distal end is frequently shortest measured cells not germline. The carrying CI-HHV-6 also prone truncations result formation...
Repressor/activator protein 1 (RAP1) is a highly evolutionarily conserved found at telomeres. Although yeast Rap1 key telomere capping preventing non-homologous end joining (NHEJ) and consequently fusions, its role mammalian telomeres in vivo still controversial. Here, we demonstrate that RAP1 required to protect replicative senescent human cells. Downregulation of these cells, but not young or dividing pre-senescent leads uncapping fusions. The anti-fusion effect was further explored HeLa...
Approximately 10% of all cancers, but a higher proportion sarcomas, use the recombination-based alternative lengthening telomeres (ALT) to maintain telomeres. Two RecQ helicase genes, BLM and WRN , play important roles in homologous recombination repair they have been implicated telomeric activity, their precise ALT are unclear. Using analysis sequence variation present human telomeres, we found that WRN– ALT+ cell line lacks class complex telomere mutations attributed inter-telomeric other...
Abstract Immortalized and cancer cells maintain their telomeres by activation of a telomere maintenance mechanism (TMM). In ∼85% cancers telomerase is activated (TA) but in some tumours, particular sarcomas, an alternative lengthening (ALT) pathway used. Liposarcomas are the most common soft‐tissue sarcoma adults they activate ALT or with equal frequency, however no TMM has been identified ∼50% liposarcomas. our study, we have shown that instability at minisatellite MS32, usually associated...
Alternative lengthening of telomere (ALT) tumors maintain telomeres by a telomerase-independent mechanism and are characterized nuclear structure called the ALT-associated PML body (APB). TRF2 is component telomeric DNA/protein complex shelterin. However, function in ALT cells remains elusive. In telomerase-positive tumor cells, inactivation results de-protection, activation ATM, consequent induction p53-dependent apoptosis. We show that this sequence events different. First,...
A number of different processes that impact on telomere length dynamics have been identified but factors affect the turnover repeats located proximally within telomeric DNA are poorly defined. We a particular repeat type (CTAGGG) is associated with an extraordinarily high mutation rate (20% per gamete) in male germline. The affected by and sequence homogeneity (CTAGGG)n array. This level instability was not seen other sequence-variant repeats, including TCAGGG has same composition. Telomeres...
DNA mismatch repair (MMR) is essential for genome stability and inheritance of a mutated MMR gene, most frequently MSH2 or MLH1, results in cancer predisposition known as Lynch syndrome hereditary nonpolyposis colorectal (HNPCC). Tumors that arise through deficiency show instability at simple tandem repeat loci (STRs) throughout the genome, microsatellite (MSI). The STR dominated by errors accumulate during replication absence effective MMR. In this study we there high level within telomeric...
The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the subunit TRF2 specialized preventing ATM activation at telomeres and chromosome end fusion somatic cells. Here, we demonstrate that zebrafish ortholog of (encoded by terfa gene) protecting against unwanted genome-wide. terfa-compromised fish develop a prominent specific embryonic neurodevelopmental failure. heterozygous survive to adulthood but exhibit premature aging phenotype....
Human telomeres shorten during each cell division, predominantly because of incomplete DNA replication. This eventually results in short uncapped that elicit a DNA-damage response, leading to cellular senescence. However, evasion senescence continued division and telomere erosion ultimately genome instability. In the long term, this instability is not sustainable, cancer cells activate TMM (telomere maintenance mechanism), either expression telomerase or activation ALT (alternative...
Abstract Aging is a continuous process leading to physiological deterioration with age. One of the factors contributing aging telomere shortening, causing alterations in protein protective complex named shelterin and replicative senescence. Here, we address question link between this shortening transcriptional changes occurring senescent cells. We found that cells, genes whose expression escaped repression are enriched subtelomeres. The TRF2 nuclear lamina factor Lamin B1, both downregulated...
Abstract Cellular senescence triggers various types of heterochromatin remodeling that contribute to aging. However, the age-related mechanisms lead these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and constitutive loss, are mechanistically connected during senescence. We show that, at onset senescence, pericentromeric is specifically dismantled consisting chromatin decondensation, accumulation DNA breakages, illegitimate...
Heterochromatic regions render the replication process particularly difficult due to high level of chromatin compaction and presence repeated DNA sequences. In humans, through pericentromeric heterochromatin requires binding a complex formed by telomeric factor TRF2 helicase RTEL1 in order relieve topological barriers blocking fork progression. Since is known bind Origin Replication Complex (ORC), we hypothesized that this could also play role at origins (ORI) these regions. By performing...
The largest economic, population, administrative, and service production of the State Puebla (east-central Mexico) is concentrated in Metropolitan Area (MAP), its effect on water quality Atoyac River substantial. anthropogenic contamination tributaries MAP was evaluated characterized. For this purpose, industry types industrial density (ID) were identified, physical–chemical urban Atoyac, Rabanillo, Zapatero Rivers, Covadonga Echeverría Dams analyzed. In addition, cytotoxicity using biomodel...
Abstract Cellular senescence triggers various types of heterochromatin remodelling that contribute to aging. However the age-ralated mechanisms lead these epigenetic alterations remain elusive. Here, we asked how two key aging hallmarks, telomere shortening and consititutive loss, are mechanistically connected during senescence. We show that, at onset senescence, pericentromeric is specifically dismantled consisting chromatin decondensation, accumulation DNA breakages, illegitimate...
Backgrounds: Cellular senescence (CS) is a response to diverse forms of nonlethal cellular stress.The phenotypic transformations occurring in CS include stable cell cycle arrest, an inflammatory response, and complex metabolic shift.Among the most prominent intrinsic stimuli are genotoxic oncogenic perturbations, many which can initiate or promote aging age-related diseases.Thus, accumulation senescent cells tissues emerges as critical driver aging.Consistently, be found affected patients...