2013
p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses
Wang Y, Sharpless N, Chang S. p16INK4a protects against dysfunctional telomere–induced ATR-dependent DNA damage responses. Journal Of Clinical Investigation 2013, 123: 4489-4501. PMID: 24091330, PMCID: PMC3784543, DOI: 10.1172/jci69574.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsApoptosisAtaxia Telangiectasia Mutated ProteinsBone Marrow TransplantationCell ProliferationCells, CulturedCyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p21DNA DamageDNA RepairDNA-Binding ProteinsFemaleHematopoiesisHematopoietic Stem CellsIntestine, SmallMaleMiceMice, SCIDMice, TransgenicProtein StabilitySequence DeletionSpleenTelomereTelomere HomeostasisTumor Suppressor Protein p53ConceptsHematopoietic cellsDeletion of p21P21-dependent cell cycle arrestOrgan impairmentTelomere dysfunctionCell cycle arrestMouse modelDNA damage responseSmall intestineFunctional defectsCell functionProliferative capacityP53-dependent apoptosisCycle arrestDysfunctional telomeresCellular senescenceDysfunctionP53-dependent DNA damage responseProliferative cellsHematopoietic systemProtective functionTumor suppressorProliferative defectP53 stabilizationCells
2008
Telomere dysfunction and tumour suppression: the senescence connection
Deng Y, Chan SS, Chang S. Telomere dysfunction and tumour suppression: the senescence connection. Nature Reviews Cancer 2008, 8: 450-458. PMID: 18500246, PMCID: PMC3688269, DOI: 10.1038/nrc2393.Peer-Reviewed Original ResearchConceptsTelomere dysfunctionDysfunctional telomeresDNA damage responseKey PointsTelomeresEukaryotic chromosomesGenome instabilityShelterin complexApoptotic programDamage responseRepetitive sequencesCellular senescenceTelomeric endTumor suppressionProtein resultsP53 pathwayMutant p53TelomeresSpontaneous tumorigenesisSenescenceTumorigenesisMouse modelChromosomesDysfunctionProteinApoptosisInitiation of Genomic Instability, Cellular Senescence, and Organismal Aging by Dysfunctional Telomeres
Chang S. Initiation of Genomic Instability, Cellular Senescence, and Organismal Aging by Dysfunctional Telomeres. 2008, 57-75. DOI: 10.1007/978-3-540-73709-4_4.Peer-Reviewed Original ResearchDysfunctional telomeresOrganismal agingCellular senescenceDNA damage responseLinear chromosomesShelterin complexDamage responseTelomeric repeatsGenomic instabilityTelomeric structureTelomeresSenescenceFunction resultsProteinImportant roleChromosomesMouse modelRepeatsTelomeraseDNAProgressive lossP53ActivationComplexesAging
2005
Modeling aging and cancer in the telomerase knockout mouse
Chang S. Modeling aging and cancer in the telomerase knockout mouse. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 2005, 576: 39-53. PMID: 15927211, DOI: 10.1016/j.mrfmmm.2004.08.020.Peer-Reviewed Original ResearchConceptsTelomere dysfunctionRole of telomeresTelomerase-null miceTelomerase knockout miceTelomerase-deficient miceOrganismal agingSomatic cellsMammalian organismsTight regulationCellular responsesTelomerase activityNull miceKnockout miceTelomeresMouse modelTelomeraseOrganismsMiceDeficient miceRegulationAgingCellsCancerModeling premature aging syndromes with the telomerase knockout mouse.
Chang S. Modeling premature aging syndromes with the telomerase knockout mouse. 2005, 5: 153-8. PMID: 15974868, DOI: 10.2174/1566524053586662.Peer-Reviewed Original ResearchConceptsTelomerase knockout miceMammalian agingGenomic instabilityDNA damage pathwayPremature aging syndromesCellular declineMolecular basisAging syndromesAging processDamage pathwayKnockout miceMolecular pathwaysShort telomeresHuman agingPrimate model systemMouse modelModel systemBiological mechanismsPhenotypePhysiological changesPathwayUnprecedented opportunityDeleterious effectsTelomeresMice
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 processTelomeresSenescenceTumorigenesisPathwayMechanismAgingCancerSyndrome