0000000000675409

AUTHOR

Fabrizio D'adda Di Fagagna

showing 5 related works from this author

Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer.

2022

: The process in which locally confined epithelial malignancies progressively evolve into invasive cancers is often promoted by unjamming, a phase transition from a solid-like to a liquid-like state, which occurs in various tissues. Whether this tissue-level mechanical transition impacts phenotypes during carcinoma progression remains unclear. Here we report that the large fluctuations in cell density that accompany unjamming result in repeated mechanical deformations of cells and nuclei. This triggers a cellular mechano-protective mechanism involving an increase in nuclear size and rigidity, heterochromatin redistribution and remodelling of the perinuclear actin architecture into actin rin…

C-gas invasive breast cancer DNA responsebreast cancercGAS-STINGSettore MED/05 - Patologia Clinicabiochemical mechanotransductionbreast cancer; cGAS-STING; DNADNASettore MED/08 - Anatomia PatologicacGAS-STING (cyclic GMP-AMP synthase-signallingNature materials
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The prolyl-isomerase PIN1 is essential for nuclear Lamin-B structure and function and protects heterochromatin under mechanical stress.

2021

Summary: Chromatin organization plays a crucial role in tissue homeostasis. Heterochromatin relaxation and consequent unscheduled mobilization of transposable elements (TEs) are emerging as key contributors of aging and aging-related pathologies, including Alzheimer’s disease (AD) and cancer. However, the mechanisms governing heterochromatin maintenance or its relaxation in pathological conditions remain poorly understood. Here we show that PIN1, the only phosphorylation-specific cis/trans prolyl isomerase, whose loss is associated with premature aging and AD, is essential to preserve heterochromatin. We demonstrate that this PIN1 function is conserved from Drosophila to humans and prevents…

transposonsNeocortexMiceHeterochromatinProlyl isomeraseDrosophila ProteinsBiology (General)PhosphorylationRNA Small InterferingTissue homeostasisCells CulturedSettore ING-INF/05 - Sistemi Di Elaborazione Delle InformazioniNeuronsLamin Type BChemistryHP1phosphorylationneurodegenerationnuclear envelopePeptidylprolyl IsomeraseCell biologyDrosophila heterochromatin HP1 Lamin mechanical stress neurodegeneration nuclear envelope phosphorylation PIN1 transposonsNuclear laminaDrosophilaRNA InterferencePremature agingQH301-705.5HeterochromatinNuclear EnvelopeDrosophila; heterochromatin; HP1; Lamin; mechanical stress; neurodegeneration; nuclear envelope; phosphorylation; PIN1; transposonsSettore BIO/11 - Biologia MolecolareSettore MED/08 - Anatomia PatologicaGeneral Biochemistry Genetics and Molecular BiologyPIN1Alzheimer DiseaseSettore MED/05 - Patologia ClinicaAnimalsHumansHeterochromatin maintenancemechanical stressheterochromatinmechanical streMice Inbred C57BLNIMA-Interacting Peptidylprolyl IsomeraseChromobox Protein Homolog 5DNA Transposable ElementsHeterochromatin protein 1Stress MechanicalLaminLaminCell reports
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Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson–Gilford Progeria Syndrome

2019

Hutchinson–Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomer…

0301 basic medicineGenome instabilityRNA UntranslatedDNA RepairGeneral Physics and AstronomyCellular homeostasisAntisense oligonucleotide therapyMice0302 clinical medicineProgeriaHomeostasislcsh:ScienceCellular SenescenceSkinProgeriaMultidisciplinaryintegumentary systemQTelomereProgerinLamin Type A3. Good healthCell biologyTelomeresPhenotypePremature agingcongenital hereditary and neonatal diseases and abnormalitiesDNA repairScienceDouble-strand DNA breaksBiologySettore MED/08 - Anatomia PatologicaGeneral Biochemistry Genetics and Molecular BiologyArticleCell Line03 medical and health sciencesmedicineDNA damage Hutchinson-Gilford Progeria SyndromeAnimalsCell Proliferationnutritional and metabolic diseasesGeneral ChemistryOligonucleotides Antisensemedicine.diseaseTelomereDisease Models Animal030104 developmental biologyMutationlcsh:Q030217 neurology & neurosurgeryLaminDNA DamageNature Communications
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DNA damage response at telomeres boosts the transcription of SARS-CoV-2 receptor ACE2 during aging

2021

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the coronavirus disease 2019 (COVID-19), known to be more common in the elderly, who also show more severe symptoms and are at higher risk of hospitalization and death. Here, we show that the expression of the angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 cell receptor, increases during aging in mouse and human lungs. ACE2 expression increases upon telomere shortening or dysfunction in both cultured mammalian cells and in vivo in mice. This increase is controlled at the transcriptional level, and Ace2 promoter activity is DNA damage response (DDR)-dependent. Both pharmacological global DDR inhibition of ATM kin…

ace2; covid-19; dna damage response; aging; telomere; aged; angiotensin-converting enzyme 2; animals; humans; mice; sars-cov-2; aging; covid-19; dna damage; telomeremiceCoronavirus disease 2019 (COVID-19)DNA damageSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)BiologySettore MED/08 - Anatomia PatologicaBiochemistry03 medical and health sciences0302 clinical medicineDownregulation and upregulationPromoter activityTranscription (biology)angiotensin-converting enzyme 2GeneticsSettore MED/05 - Patologia ClinicaReceptorhumansMolecular Biology030304 developmental biology0303 health sciencestelomereAce2 aging COVID-19DNA damage response telomereagingace23. Good healthTelomereCell biologybody regionsdna damage responseanimalsagedsars-cov-2covid-19Angiotensin-converting enzyme 2Cancer researchdna damagehormones hormone substitutes and hormone antagonists030217 neurology & neurosurgery
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From “Cellular” RNA to “Smart” RNA: Multiple Roles of RNA in Genome Stability and Beyond

2018

Coding for proteins has been considered the main function of RNA since the "central dogma" of biology was proposed. The discovery of noncoding transcripts shed light on additional roles of RNA, ranging from the support of polypeptide synthesis, to the assembly of subnuclear structures, to gene expression modulation. Cellular RNA has therefore been recognized as a central player in often unanticipated biological processes, including genomic stability. This ever-expanding list of functions inspired us to think of RNA as a "smart" phone, which has replaced the older obsolete "cellular" phone. In this review, we summarize the last two decades of advances in research on the interface between RNA…

0301 basic medicineGenome instabilityRegulation of gene expressionRNA UntranslatedTranscription GeneticChemistryRNA-Binding ProteinsRNARNA-binding proteinGeneral ChemistryComputational biologyNon-coding RNAArticleGenomic Instability03 medical and health sciences030104 developmental biologyGene Expression RegulationTranscription (biology)RNA interferenceGene expressionHumans570 Life sciences; biologyDNA Breaks Double-StrandedRNA InterferenceDNA Damage
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