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 ResearchTRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions
Rai R, Chen Y, Lei M, Chang S. TRF2-RAP1 is required to protect telomeres from engaging in homologous recombination-mediated deletions and fusions. Nature Communications 2016, 7: 10881. PMID: 26941064, PMCID: PMC4785230, DOI: 10.1038/ncomms10881.Peer-Reviewed Original ResearchConceptsRepressor/activator protein 1Telomere length controlTranscriptional gene regulationRepair of telomeresTelomere end protectionNon-homologous endActivator protein-1Myb domainChromosome fusionsYeast Rap1Gene regulationHDR pathwayEnd protectionBasic domainTelomere lossTelomeresHuman cellsHR factorsProtein 1Length controlPARP1Free fusionInappropriate processingTRF2Important role
2012
CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion
Gu P, Min J, Wang Y, Huang C, Peng T, Chai W, Chang S. CTC1 deletion results in defective telomere replication, leading to catastrophic telomere loss and stem cell exhaustion. The EMBO Journal 2012, 31: 2309-2321. PMID: 22531781, PMCID: PMC3364752, DOI: 10.1038/emboj.2012.96.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA ReplicationGene DeletionMiceMice, KnockoutStem CellsTelomereTelomere-Binding ProteinsConceptsMammalian CSTTelomere lossDefective telomere replicationDeletion resultsG2/M checkpointComplete bone marrow failureStem cell exhaustionTelomere deprotectionGenome stabilityTEN1 (CST) complexTelomere replicationReplication forksTelomere maintenanceLength maintenanceCTC1-STN1Efficient restartM checkpointVivo functionCTC1TelomeresAcute deletionBone marrow failureProliferative defectEfficient replicationEssential role
2009
Gcn5 and SAGA Regulate Shelterin Protein Turnover and Telomere Maintenance
Atanassov BS, Evrard YA, Multani AS, Zhang Z, Tora L, Devys D, Chang S, Dent SY. Gcn5 and SAGA Regulate Shelterin Protein Turnover and Telomere Maintenance. Molecular Cell 2009, 35: 352-364. PMID: 19683498, PMCID: PMC2749492, DOI: 10.1016/j.molcel.2009.06.015.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedChromosome AberrationsDNA Breaks, Double-StrandedDNA RepairGene DeletionHumansMiceModels, BiologicalP300-CBP Transcription FactorsProteasome InhibitorsProtein StabilityShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 1Thiolester HydrolasesUbiquitin ThiolesteraseConceptsSAGA complexTelomeric shelterin complexDeletion of GCN5Accessibility of chromatinBona fide componentTRF1 levelsGene regulationShelterin complexTelomere maintenanceMammalian cellsTranscription factorsGCN5DNA repairFide componentRepair proteinsTelomere dysfunctionProtein turnoverHuman cellsUbiquitin-specific protease 22Biochemical studiesOverexpression of USP22USP22ComplexesTurnoverChromatinPot1b 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
2002
Telomere dysfunction provokes regional amplification and deletion in cancer genomes
O'Hagan R, Chang S, Maser R, Mohan R, Artandi S, Chin L, DePinho R. Telomere dysfunction provokes regional amplification and deletion in cancer genomes. Cancer Cell 2002, 2: 149-155. PMID: 12204535, DOI: 10.1016/s1535-6108(02)00094-6.Peer-Reviewed Original ResearchConceptsTelomere dysfunctionAged humansMajor cancersPathogenic significanceDysfunctionEpithelial carcinogenesisArray comparative genomic hybridizationComparative genomic hybridizationCancer hotspotsGenomic profilesNonreciprocal translocationsTumorsMiceCarcinogenesisGenomic hybridizationChromosomal instability