2016
Dysfunctional telomeres induce p53‐dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation
Wang Y, Wang X, Flores ER, Yu J, Chang S. Dysfunctional telomeres induce p53‐dependent and independent apoptosis to compromise cellular proliferation and inhibit tumor formation. Aging Cell 2016, 15: 646-660. PMID: 27113195, PMCID: PMC4933665, DOI: 10.1111/acel.12476.Peer-Reviewed Original Research
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
2010
The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development
Akhter S, Lam YC, Chang S, Legerski RJ. The telomeric protein SNM1B/Apollo is required for normal cell proliferation and embryonic development. Aging Cell 2010, 9: 1047-1056. PMID: 20854421, PMCID: PMC3719988, DOI: 10.1111/j.1474-9726.2010.00631.x.Peer-Reviewed Original ResearchConceptsMutant mouse embryonic fibroblastsSNM1B/ApolloCell proliferation defectMouse embryonic fibroblastsNormal cell proliferationDevelopmental failureHomozygous null miceEnd fusionsProliferation defectEmbryonic developmentGenomic instabilityEmbryonic fibroblastsTelomeric endDevelopmental defectsCell deathVivo roleCell proliferationImpaired proliferationTelomeresNull miceMutant miceAurora Kinase A Promotes Ovarian Tumorigenesis through Dysregulation of the Cell Cycle and Suppression of BRCA2
Yang G, Chang B, Yang F, Guo X, Cai K, Xiao X, Wang H, Sen S, Hung M, Mills G, Chang S, Multani A, Mercado-Uribe I, Liu J. Aurora Kinase A Promotes Ovarian Tumorigenesis through Dysregulation of the Cell Cycle and Suppression of BRCA2. Clinical Cancer Research 2010, 16: 3171-3181. PMID: 20423983, PMCID: PMC2930838, DOI: 10.1158/1078-0432.ccr-09-3171.Peer-Reviewed Original ResearchConceptsDNA damage responseGenomic instabilitySmall hairpin RNADamage responseExpression ratioCell cycle progressionOvarian cancer cell line SKOV3Multiple human cancersColon cancer samplesKnockdown of AuroraCell cycle alterationsMitotic spindleCell cycle dysregulationCell line SKOV3Cycle progressionExpression of AuroraMolecular mechanismsCell cycleAurora kinasesHairpin RNATumor growthCentrosome amplificationHuman cancersHuman ovarian cancerHigh-grade ovarian serous carcinoma
2009
Pot1b Deletion and Telomerase Haploinsufficiency in Mice Initiate an ATR-Dependent DNA Damage Response and Elicit Phenotypes Resembling Dyskeratosis Congenita
He H, Wang Y, Guo X, Ramchandani S, Ma J, Shen MF, Garcia DA, Deng Y, Multani AS, You MJ, Chang S. Pot1b Deletion and Telomerase Haploinsufficiency in Mice Initiate an ATR-Dependent DNA Damage Response and Elicit Phenotypes Resembling Dyskeratosis Congenita. Molecular And Cellular Biology 2009, 29: 229-240. PMID: 18936156, PMCID: PMC2612488, DOI: 10.1128/mcb.01400-08.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsBone Marrow CellsCell Cycle ProteinsCell DeathCell ProliferationDNA DamageDNA-Binding ProteinsDyskeratosis CongenitaGene DeletionHaploidyHematopoietic SystemMiceMice, KnockoutNucleic Acid ConformationOrgan SpecificityPhenotypeProtein Serine-Threonine KinasesSurvival AnalysisTelomeraseTelomereConceptsDisease dyskeratosis congenitaATR-dependent DNA damage responseDNA damage responseTelomerase haploinsufficiencyDamage responseBone marrow failureTelomeres 1 (POT1) proteinDyskeratosis congenitaProliferative tissueGenome integrityPOT1 functionChromosome endsMarrow failureEnd fusionsG-overhangsChromosome instabilityTelomerase deficiencyGerm cellsBinding proteinHematopoietic progenitorsStem cellsSurvival potentialEssential roleLong-term viabilityCellular viability
2008
Mre11 Nuclease Activity Has Essential Roles in DNA Repair and Genomic Stability Distinct from ATM Activation
Buis J, Wu Y, Deng Y, Leddon J, Westfield G, Eckersdorff M, Sekiguchi JM, Chang S, Ferguson DO. Mre11 Nuclease Activity Has Essential Roles in DNA Repair and Genomic Stability Distinct from ATM Activation. Cell 2008, 135: 85-96. PMID: 18854157, PMCID: PMC2645868, DOI: 10.1016/j.cell.2008.08.015.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell Line, TransformedCell ProliferationDNA Breaks, Double-StrandedDNA DamageDNA RepairDNA Repair EnzymesDNA-Binding ProteinsFibroblastsGenomic InstabilityMiceMRE11 Homologue ProteinProtein Serine-Threonine KinasesRecombination, GeneticTelomereTumor Suppressor ProteinsConceptsMre11/Rad50/Nbs1Nuclease activityDNA repairDNA damageDramatic genomic instabilityFunctions of Mre11Early embryonic lethalityMre11 nuclease activityATM kinaseATR kinaseEmbryonic lethalityGenomic stabilityATM activationMRN complexNucleolytic processingBreak repairDNA endsATM signalingMouse alleleGenomic instabilityDNA nuclease activityNuclease deficienciesEssential functionsUnknown roleMre11Critical and Distinct Roles of p16 and Telomerase in Regulating the Proliferative Life Span of Normal Human Prostate Epithelial Progenitor Cells*
Bhatia B, Jiang M, Suraneni M, Patrawala L, Badeaux M, Schneider-Broussard R, Multani AS, Jeter CR, Calhoun-Davis T, Hu L, Hu J, Tsavachidis S, Zhang W, Chang S, Hayward SW, Tang DG. Critical and Distinct Roles of p16 and Telomerase in Regulating the Proliferative Life Span of Normal Human Prostate Epithelial Progenitor Cells*. Journal Of Biological Chemistry 2008, 283: 27957-27972. PMID: 18662989, PMCID: PMC2562067, DOI: 10.1074/jbc.m803467200.Peer-Reviewed Original ResearchConceptsProliferative life spanNHP cellsMolecular mechanismsProgenitor cellsSuppression of p16Normal human prostate epithelial cellsGene expression profilesLife spanProstate epithelial progenitor cellsHuman prostate epithelial cellsRegulation of p16Activation of p53Prostate epithelial cellsEpithelial progenitor cellsCell proliferative capacityExpression profilesBasal-like cellsProgenitor markersMultilineage differentiationTelomerase expressionDistinct rolesCell life spanCell marker CD44P16 inhibitionEpithelial cells