A5056129637- Telomeres, Telomerase, and Senescence
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Chromosomal and Genetic Variations
- Genomics and Chromatin Dynamics
- Neonatal Respiratory Health Research
- Genetics, Aging, and Longevity in Model Organisms
- Nuclear Structure and Function
- Epigenetics and DNA Methylation
- Estrogen and related hormone effects
- Reproductive System and Pregnancy
- Mitochondrial Function and Pathology
- Air Quality and Health Impacts
- RNA and protein synthesis mechanisms
- Ubiquitin and proteasome pathways
- Adipokines, Inflammation, and Metabolic Diseases
- Digestive system and related health
- Adipose Tissue and Metabolism
- RNA Interference and Gene Delivery
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Mechanisms of cancer metastasis
- Endometriosis Research and Treatment
- NF-κB Signaling Pathways
- Pluripotent Stem Cells Research
- RNA Research and Splicing
Inserm
2013-2025
Centre de Recherche en Cancérologie de Marseille
2016-2025
Aix-Marseille Université
2013-2025
Centre National de la Recherche Scientifique
2013-2025
La Ligue Contre le Cancer
2021-2024
Institut Paoli-Calmettes
2016-2021
Institut Pprime
2021
Cancer Research Center
2020
University of Cincinnati
2009
University of Cincinnati Medical Center
2006-2008
BACKGROUND: In this prospective randomized blinded clinical trial, we examined gene expression profiles of the human endometrium during early and mid-luteal phases natural cycle. METHODS: An endometrial biopsy was performed on day 16 (LH +3) or 21 +8), followed by RNA extraction microarray analysis using an Affymetrix HG-U95A microchip. Data carried out pairwise multiple group comparison with significance microarrays (SAM) software. RESULTS: With a false discovery rate 0, revealed that 107...
Highlights•SUMO modification accumulates at eroded telomeres after loss of telomerase•SUMOlyation promotes recruitment Slx5-Slx8 STUbL to telomeres•Rfa1 is SUMOylated during telomere erosion and physically interacts with Slx5•STUbL-dependent targeting NPCs type II recombinationSummaryIn budding yeast, inactivation telomerase ensuing cause relocalization nuclear pore complexes (NPCs). However, neither the mechanism such nor its significance are understood. We report that proteins bound...
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...
Abstract The Nuclear Pore Complex (NPC) has emerged as an important hub for processing various types of DNA damage. Here, we uncover that fusing a binding domain to the NPC basket protein Nup1 reduces telomere relocalization nuclear pores early after telomerase inactivation. This modification also impairs expanded CAG/CTG triplet repeats. Strikingly, negative cells bypass senescence when expressing this by maintaining minimal length compatible with proliferation through rampant unequal...
Ubiquitin-fold modifier 1 (UFM1) is involved in neural and erythroid development, yet its biological roles these processes are unknown. Here, we generated zebrafish models deficient Ufm1 Ufl1 that exhibited telomere shortening associated with developmental delay, impaired hematopoiesis premature aging. We further report HeLa cells lacking UFL1 have instability of telomeres replicated by leading-strand synthesis. uncover MRE11 UFMylation necessary for the recruitment phosphatase PP1-α leading...
Inherited bone marrow failure syndromes (IBMFSs) are a group of disorders typified by impaired production 1 or several blood cell types. The telomere biology dyskeratosis congenita (DC) and its severe variant, Høyeraal-Hreidarsson (HH) syndrome, rare IBMFSs characterized failure, developmental defects, various premature aging complications associated with critically short telomeres. We identified biallelic variants in the gene encoding 5'-to-3' DNA exonuclease Apollo/SNM1B 3 unrelated...
Abstract Lung diseases develop when telomeres shorten beyond a critical point. We constructed mouse model in which the catalytic subunit of telomerase (mTert), or its catalytically inactive form (mTert CI ), is expressed from p21 Cdkn1a locus. Expression either TERT reduces global levels lungs aged mice, highlighting non-canonical function. However, only accumulation very short telomeres, oxidative damage, endothelial cell (ECs) senescence and senile emphysema mice. Single-cell analysis lung...
Although vertebrate POT1 is thought to play a role in both telomere capping and length regulation, its function has proved difficult analyze. We therefore generated conditional cell line that lacks wild-type but expresses an estrogen receptor-POT1 fusion. The cells grow normally tamoxifen, drug removal causes loss of from the telomere, rapid cycle arrest, eventual death. arrested have 4N DNA content, addition caffeine immediate entry into mitosis, suggesting G(2) arrest due ATM- and/or...
Telomerase-negative yeasts survive via one of the two Rad52-dependent recombination pathways, which have distinct genetic requirements. Although telomere pattern type I and II survivors is well characterized, mechanistic details short rearrangement into highly evolved observed in are still missing. Here, we analyze immediate events taking place at abruptly shortened VII-L native telomeres. We show that telomeres engage pairing with internal Rap1-bound TG1–3-like tracts present between...
Abstract Obesity is linked to limited adipose tissue (AT) remodeling capacity, leading hypertrophic adipocytes, senescence, and inflammation. We used a mouse model expressing mTert (p21 +/Tert ) from the Cdkn1a locus investigate role of mTERT in obesity-induced metabolic disorders. Conditional expression reduces disorders associated with obesity. In AT, this accompanied by decrease number senescent p21-positive cells, very short telomeres, oxidative DNA damage. Single nucleus RNA-seq data...
MINI REVIEW article Front. Oncol., 28 February 2013Sec. Cancer Molecular Targets and Therapeutics Volume 3 - 2013 | https://doi.org/10.3389/fonc.2013.00039
Replicative senescence is triggered by short unprotected telomeres that arise in the absence of telomerase. In addition, are known as difficult regions to replicate due their repetitive G-rich sequence prone secondary structures and tightly bound non-histone proteins. Here we review accumulating evidence telomerase inactivation yeast immediately unmasks problems associated with replication stress at telomeres. Early after inactivation, cells undergo successive rounds stochastic DNA damages...
Functional telomeres in yeast lacking telomerase can be restored by rare Rad51- or Rad59-dependent recombination events that lead to type I and II survivors, respectively. We previously proposed polySUMOylation of proteins the SUMO-targeted ubiquitin ligase Slx5-Slx8 are key factors recombination. Here, we show SUMOylation Rad52 favors formation survivors. Conversely, preventing partially bypasses requirement for further report SUMO-dependent proteasomal degradation Finally, inactivation...
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...
Abstract Genetic studies using knockout mouse models provide strong evidence for the essential role of ubiquitin-like protein UFM1 hematopoiesis, especially erythroid development, yet its biological roles in this process are largely unknown. Here we have identified a UFL1-dependent UFMylation MRE11 nuclease on K281 and K282 residues. We show that Hela cells lacking specific E3 ligase display severe telomere shortening. further demonstrate either by deleting or mutating sites preventing...