2017
Probing the Telomere Damage Response
Rai R, Chang S. Probing the Telomere Damage Response. Methods In Molecular Biology 2017, 1587: 133-138. PMID: 28324505, DOI: 10.1007/978-1-4939-6892-3_13.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCells, CulturedDNADNA Breaks, Double-StrandedDNA DamageDNA RepairDNA-Binding ProteinsHEK293 CellsHumansMiceSignal TransductionTelomereTumor Suppressor p53-Binding Protein 1ConceptsTelomere dysfunctionDNA damage response signalsDNA damage repair pathwaysTelomere damage responseΓ-H2AXDamage repair pathwaysCheckpoint sensorNbs1 complexReplicative attritionMre11-Rad50Shelterin componentsDamage responseTelomeric DNADysfunctional telomeresRepair pathwaysDownstream effectorsComplete deletionTelomeresDNAPathwayTRF2Chk2Chk1KinaseEffectorsNBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres
Rai R, Hu C, Broton C, Chen Y, Lei M, Chang S. NBS1 Phosphorylation Status Dictates Repair Choice of Dysfunctional Telomeres. Molecular Cell 2017, 65: 801-817.e4. PMID: 28216226, PMCID: PMC5639704, DOI: 10.1016/j.molcel.2017.01.016.Peer-Reviewed Original ResearchAminopeptidasesAtaxia Telangiectasia Mutated ProteinsBinding SitesCell Cycle ProteinsCyclin-Dependent Kinase 2Dipeptidyl-Peptidases and Tripeptidyl-PeptidasesDNA Breaks, Double-StrandedDNA End-Joining RepairDNA Repair EnzymesDNA-Binding ProteinsExodeoxyribonucleasesG1 PhaseG2 PhaseHCT116 CellsHumansInhibitor of Apoptosis ProteinsModels, MolecularNuclear ProteinsPhosphorylationProtein BindingProtein Interaction Domains and MotifsS PhaseSerine ProteasesShelterin ComplexStructure-Activity RelationshipTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2
2014
Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss
Lee Y, Brown EJ, Chang S, McKinnon PJ. Pot1a Prevents Telomere Dysfunction and ATM-Dependent Neuronal Loss. Journal Of Neuroscience 2014, 34: 7836-7844. PMID: 24899707, PMCID: PMC4044246, DOI: 10.1523/jneurosci.4245-13.2014.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornAtaxia Telangiectasia Mutated ProteinsBeta-GalactosidaseBrainCell CycleCell Cycle ProteinsCells, CulturedDNA DamageDNA-Binding ProteinsEmbryo, MammalianFemaleGene Expression RegulationMaleMiceMice, TransgenicNestinNeuronsShelterin ComplexTelomereTelomere-Binding Proteins
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
2012
Chromosome ends teach unexpected lessons on DNA damage signalling
Chang S. Chromosome ends teach unexpected lessons on DNA damage signalling. The EMBO Journal 2012, 31: 3380-3381. PMID: 22842787, PMCID: PMC3419931, DOI: 10.1038/emboj.2012.199.Peer-Reviewed Original ResearchMeSH KeywordsAtaxia Telangiectasia Mutated ProteinsCdc25 PhosphatasesCell Cycle ProteinsCytokinesisDNA-Binding ProteinsGene Expression RegulationHumansProtein Serine-Threonine KinasesTelomereTumor Suppressor ProteinsRPA and POT1
Flynn RL, Chang S, Zou L. RPA and POT1. Cell Cycle 2012, 11: 652-657. PMID: 22373525, PMCID: PMC3318101, DOI: 10.4161/cc.11.4.19061.Peer-Reviewed Original ResearchMeSH KeywordsAtaxia Telangiectasia Mutated ProteinsCell CycleCell Cycle ProteinsHumansModels, BiologicalProtein Serine-Threonine KinasesReplication Protein AShelterin ComplexTelomereTelomere-Binding ProteinsConceptsReplication protein ATelomere maintenanceDNA replicationProtein complex shelterinTTAGGG telomeric repeatsTelomeric ssDNACheckpoint responseTelomeric repeatsPOT1Ataxia telangiectasiaCell cycleAberrant accumulationCycling cellsSpecific mannerInteresting modelTelomeresProtein ACritical roleProteinRecent studiesReplicationShelterinRad3KinaseRepeats
2011
TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA
Flynn RL, Centore RC, O’Sullivan R, Rai R, Tse A, Songyang Z, Chang S, Karlseder J, Zou L. TERRA and hnRNPA1 orchestrate an RPA-to-POT1 switch on telomeric single-stranded DNA. Nature 2011, 471: 532-536. PMID: 21399625, PMCID: PMC3078637, DOI: 10.1038/nature09772.Peer-Reviewed Original ResearchAtaxia Telangiectasia Mutated ProteinsBinding, CompetitiveCell Cycle ProteinsCell ExtractsDNA ReplicationDNA, Single-StrandedHeLa CellsHeterogeneous Nuclear Ribonucleoprotein A1Heterogeneous-Nuclear Ribonucleoprotein Group A-BHumansProtein BindingReplication Protein ARNAS PhaseShelterin ComplexTelomereTelomere-Binding ProteinsThe RAG2 C terminus suppresses genomic instability and lymphomagenesis
Deriano L, Chaumeil J, Coussens M, Multani A, Chou Y, Alekseyenko AV, Chang S, Skok JA, Roth DB. The RAG2 C terminus suppresses genomic instability and lymphomagenesis. Nature 2011, 471: 119-123. PMID: 21368836, PMCID: PMC3174233, DOI: 10.1038/nature09755.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsChromosome DeletionChromosomes, MammalianDisease ProgressionDNA-Binding ProteinsGene Rearrangement, T-LymphocyteGenes, Immunoglobulin Heavy ChainGenes, p53Genomic InstabilityIn Situ Hybridization, FluorescenceKaplan-Meier EstimateLymphomaMiceProtein Serine-Threonine KinasesReceptors, Antigen, T-CellRecombination, GeneticThymus GlandTranslocation, GeneticTumor Suppressor ProteinsConceptsRAG2 C terminusGenomic instabilityC-terminusTCRα/δDNA double-strand breaksT-cell receptor lociDouble-strand breaksGenomic stabilityComplex chromosomal translocationReceptor locusChromosomal translocationsSimilar defectsLymphomagenesisThymic lymphomasTerminusLociRecombinaseTailRAG2TranslocationDeletionRecombinationRoleLymphoid malignanciesMice
2010
SNMIB/Apollo protects leading‐strand telomeres against NHEJ‐mediated repair
Lam YC, Akhter S, Gu P, Ye J, Poulet A, Giraud‐Panis M, Bailey SM, Gilson E, Legerski RJ, Chang S. SNMIB/Apollo protects leading‐strand telomeres against NHEJ‐mediated repair. The EMBO Journal 2010, 29: 2230-2241. PMID: 20551906, PMCID: PMC2905253, DOI: 10.1038/emboj.2010.58.Peer-Reviewed Original ResearchMeSH KeywordsAminopeptidasesAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsChromosomesDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDNA DamageDNA RepairDNA-Binding ProteinsEmbryo, MammalianExodeoxyribonucleasesFibroblastsMiceMice, KnockoutProtein Serine-Threonine KinasesSerine ProteasesShelterin ComplexTelomereTelomere-Binding ProteinsTripeptidyl-Peptidase 1Tumor Suppressor ProteinsConceptsMouse embryo fibroblastsNull mouse embryo fibroblastsNon-homologous end-joining pathwayLeading-strand DNA synthesisExonuclease functionSNM1B/ApolloDNA double-strand breaksDNA damage responseEnd-joining pathwayDouble-strand breaksMammalian telomeresUncapped telomeresNuclease domainNuclease familyDamage responseDNA replicationTelomeric endTelomeresNuclease activity
2009
Multiple roles for MRE11 at uncapped telomeres
Deng Y, Guo X, Ferguson DO, Chang S. Multiple roles for MRE11 at uncapped telomeres. Nature 2009, 460: 914-918. PMID: 19633651, PMCID: PMC2760383, DOI: 10.1038/nature08196.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsATP-Binding Cassette TransportersCell Cycle ProteinsCell LineChromosomal Proteins, Non-HistoneChromosome AberrationsDNA DamageDNA Ligase ATPDNA LigasesDNA Repair EnzymesDNA-Binding ProteinsFibroblastsIntracellular Signaling Peptides and ProteinsMiceMRE11 Homologue ProteinNuclear ProteinsShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2Tumor Suppressor p53-Binding Protein 1Tumor Suppressor ProteinsConceptsMRN complexLinear eukaryotic chromosomesDNA double-strand breaksDNA damage repair pathwaysDouble-strand breaksDamage repair pathwaysGenome integrityEukaryotic chromosomesUncapped telomeresTelomere maintenanceRepair factorsDNA endsRepair pathwaysTelomeric endNuclease activityTelomeresMultiple rolesMre11Major playersPathogenic lesionsMre1ChromosomesComplexesProteinAllelesPot1b 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 roleMre11
2007
Dysfunctional telomeres activate an ATM‐ATR‐dependent DNA damage response to suppress tumorigenesis
Guo X, Deng Y, Lin Y, Cosme‐Blanco W, Chan S, He H, Yuan G, Brown EJ, Chang S. Dysfunctional telomeres activate an ATM‐ATR‐dependent DNA damage response to suppress tumorigenesis. The EMBO Journal 2007, 26: 4709-4719. PMID: 17948054, PMCID: PMC2080807, DOI: 10.1038/sj.emboj.7601893.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCells, CulturedDNA DamageDNA-Binding ProteinsEmbryo, MammalianFibroblastsMiceNeoplasmsProtein Serine-Threonine KinasesRNA, MessengerShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2Tumor Suppressor Proteins