2019
NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome
Fang EF, Hou Y, Lautrup S, Jensen MB, Yang B, SenGupta T, Caponio D, Khezri R, Demarest TG, Aman Y, Figueroa D, Morevati M, Lee HJ, Kato H, Kassahun H, Lee JH, Filippelli D, Okur MN, Mangerich A, Croteau DL, Maezawa Y, Lyssiotis CA, Tao J, Yokote K, Rusten TE, Mattson MP, Jasper H, Nilsen H, Bohr VA. NAD+ augmentation restores mitophagy and limits accelerated aging in Werner syndrome. Nature Communications 2019, 10: 5284. PMID: 31754102, PMCID: PMC6872719, DOI: 10.1038/s41467-019-13172-8.Peer-Reviewed Original ResearchMeSH KeywordsAging, PrematureAnimalsAutophagy-Related Protein-1 HomologCaenorhabditis elegansCation Transport ProteinsDisease Models, AnimalDrosophila melanogasterHumansIntracellular Signaling Peptides and ProteinsMitophagyMutationNADNicotinamide-Nucleotide AdenylyltransferaseWerner SyndromeWerner Syndrome HelicaseConceptsWerner syndromeWerner DNA helicasePremature aging diseaseDrosophila melanogaster modelStem cell dysfunctionCaenorhabditis elegansDNA helicaseOrganismal levelImpaired mitochondrial functionMitochondrial qualityWS phenotypeImpaired mitophagyMitophagyMitochondrial functionDCT-1Ubiquitous moleculeSevere metabolic phenotypeMetabolic phenotypePhenotypeW patientsMetabolic dysfunctionCell dysfunctionMetabolic deficitsTherapeutic interventionsUnderlying mechanism
2007
WRN at telomeres: implications for aging and cancer
Multani AS, Chang S. WRN at telomeres: implications for aging and cancer. Journal Of Cell Science 2007, 120: 713-721. PMID: 17314245, DOI: 10.1242/jcs.03397.Peer-Reviewed Original ResearchConceptsWerner syndromeHuman Werner syndromePremature aging syndromesRecent genetic evidenceAge-related pathologiesGenome stabilityWRN deficiencyTelomere maintenanceDNA replicationGenetic evidenceSingle gene defectsTelomere dysfunctionCellular senescenceAging syndromesMolecular levelPremature agingEarly cancer onsetWRNGene defectsCancer onsetMajor roleTelomeresSenescenceRapid onsetProtein
2005
Werner Protein Protects Nonproliferating Cells from Oxidative DNA Damage
Szekely AM, Bleichert F, Nümann A, Van Komen S, Manasanch E, Nasr A, Canaan A, Weissman SM. Werner Protein Protects Nonproliferating Cells from Oxidative DNA Damage. Molecular And Cellular Biology 2005, 25: 10492-10506. PMID: 16287861, PMCID: PMC1291253, DOI: 10.1128/mcb.25.23.10492-10506.2005.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesCell ProliferationCells, CulturedCellular SenescenceDNADNA DamageDNA HelicasesDNA ReplicationExodeoxyribonucleasesFibroblastsGene Expression RegulationHumansOxidation-ReductionOxidative StressOxygenRecQ HelicasesRNA InterferenceTelomeric Repeat Binding Protein 2Werner Syndrome HelicaseConceptsDNA damage responseWerner syndromeDamage responseDNA damageRNA interferenceOxidative DNA damageWRN-depleted cellsInduction of gammaH2AXDNA damage fociCellular senescence phenotypePrimary human fibroblastsWRN depletionWerner proteinWRN proteinNuclear fociWRN deficiencyProtein TRF2Telomere maintenanceAcute oxidative stressBLM expressionDNA homeostasisDNA replicationDamage fociSenescence phenotypePhysiological oxygenElevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway
Laud PR, Multani AS, Bailey SM, Wu L, Ma J, Kingsley C, Lebel M, Pathak S, DePinho RA, Chang S. Elevated telomere-telomere recombination in WRN-deficient, telomere dysfunctional cells promotes escape from senescence and engagement of the ALT pathway. Genes & Development 2005, 19: 2560-2570. PMID: 16264192, PMCID: PMC1276730, DOI: 10.1101/gad.1321305.Peer-Reviewed Original ResearchConceptsWerner syndromeSister chromatidsT-SCETelomere sister chromatid exchangeElevated recombination ratesActivation of ALTWRN functionAberrant recombinationGenomic instabilityALT pathwayChromosomal aberrationsChromosomal instabilityTelomeresPremature agingDysfunctional cellsTumor formationChromatidsSister chromatid exchangesPathwayChromatid exchangesRecombinationRecombination rateCellsWRNMutants
2004
A mouse model of Werner Syndrome: what can it tell us about aging and cancer?
Chang S. A mouse model of Werner Syndrome: what can it tell us about aging and cancer? The International Journal Of Biochemistry & Cell Biology 2004, 37: 991-999. PMID: 15743673, DOI: 10.1016/j.biocel.2004.11.007.Peer-Reviewed Original ResearchConceptsMolecular mechanismsWerner syndromePremature agingConsequent cellular responsesGene functionMammalian agingDysfunctional telomeresGenetic pathwaysReplicative senescenceTelomere dysfunctionCellular responsesGenetic platformProgeroid syndromesMolecular levelMouse modelRecent studiesAging processTelomeresSenescenceTumorigenesisPathwayMechanismAgingCancerSyndromeEssential role of limiting telomeres in the pathogenesis of Werner syndrome
Chang S, Multani AS, Cabrera NG, Naylor ML, Laud P, Lombard D, Pathak S, Guarente L, DePinho RA. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nature Genetics 2004, 36: 877-882. PMID: 15235603, DOI: 10.1038/ng1389.Peer-Reviewed Original ResearchConceptsWerner syndromeCultured cellsComplex cellular phenotypesElevated genomic instabilityDNA damage fociPremature aging syndromesWRN deficiencyReplicative senescenceCellular phenotypesGenomic instabilityAging syndromesGenetic dataMutational inactivationPremature senescenceChromosomal instabilityTelomerase expressionHair grayingPremature agingDisease phenotypeEssential roleWRNMice nullSenescenceAutosomal recessive diseaseType II diabetes
2000
Werner protein recruits DNA polymerase δ to the nucleolus
Szekely A, Chen Y, Zhang C, Oshima J, Weissman S. Werner protein recruits DNA polymerase δ to the nucleolus. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 11365-11370. PMID: 11027336, PMCID: PMC17206, DOI: 10.1073/pnas.97.21.11365.Peer-Reviewed Original ResearchConceptsWerner proteinWRN proteinDNA replicationPolymerase deltaChromosomal DNA replicationTwo-hybrid screeningSubcellular localization studiesDNA polymerase δMajor DNA polymeraseDNA helicasesRecQ familyDNA transactionsDynamic relocalizationNucleolar proteinsCatalytic subunitPolymerase δC-terminusWRN geneWerner syndromeExonuclease activityPhysiological functionsMendelian disordersLocalization studiesLines of evidenceDNA polymerase
1996
Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells
Schulz V, Zakian V, Ogburn C, McKay J, Jarzebowicz A, Martin G, Edland S. Accelerated loss of telomeric repeats may not explain accelerated replicative decline of Werner syndrome cells. Human Genetics 1996, 97: 750-754. PMID: 8641691, DOI: 10.1007/bf02346184.Peer-Reviewed Original ResearchConceptsTRF lengthMean TRF lengthWerner syndromeDiabetes mellitusControl subjectsWS cellsReplicative declineSubset of cellsOcular cataractsGeriatric disordersPremature onsetMean lengthSenescent controlsReplicative capacitySenescent cellsEarly passagesAccelerated lossAccelerated rateChromosomal translocationsNormal somatic cellsWerner syndrome cellsReplicative potentialCellsCell cycle
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