2023
Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2B and RAP1
Rai R, Biju K, Sun W, Sodeinde T, Al-Hiyasat A, Morgan J, Ye X, Li X, Chen Y, Chang S. Homology directed telomere clustering, ultrabright telomere formation and nuclear envelope rupture in cells lacking TRF2B and RAP1. Nature Communications 2023, 14: 2144. PMID: 37059728, PMCID: PMC10104862, DOI: 10.1038/s41467-023-37761-w.Peer-Reviewed Original ResearchConceptsDouble-strand breaksNuclear envelopeDistinct DNA repair mechanismsNuclear envelope ruptureKu70/Ku80DNA repair mechanismsDNA-RNA hybridsBRCT domainGenome stabilityPhosphomimetic mutantTelomere formationGenotoxic stressEnvelope ruptureDysfunctional telomeresBasic domainRap1Aberrant laminTelomeresRepair mechanismsLaminsTRF2HomologyProteinShelterinADAR1p110
2013
The mINO80 chromatin remodeling complex is required for efficient telomere replication and maintenance of genome stability
Min JN, Tian Y, Xiao Y, Wu L, Li L, Chang S. The mINO80 chromatin remodeling complex is required for efficient telomere replication and maintenance of genome stability. Cell Research 2013, 23: 1396-1413. PMID: 23979016, PMCID: PMC3847565, DOI: 10.1038/cr.2013.113.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsCells, CulturedCellular SenescenceChromatinChromatin Assembly and DisassemblyDNA Breaks, Double-StrandedDNA HelicasesDNA RepairDNA ReplicationFibroblastsGenomic InstabilityHydroxyureaMiceMice, Inbred C57BLMice, KnockoutMutationNucleic Acid Synthesis InhibitorsTelomereTumor Suppressor Protein p53ConceptsHomology-directed DNA repairEfficient telomere replicationGenome stabilityTelomere replicationDependent DNA damage responseDNA double-strand breaksDNA damage responseDNA damage fociMammalian cell linesATPase catalytic subunitConditional knockout approachDouble-strand breaksINO80 chromatinChromatin remodelingOrganismal functionTranscriptional regulationFragile telomeresDamage responseDNA replicationCatalytic subunitDamage fociDysfunctional telomeresSingle-strand DNADNA repairKnockout approach
2011
The 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 activityBRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice
Liang Y, Gao H, Lin S, Peng G, Huang X, Zhang P, Goss J, Brunicardi F, Multani A, Chang S, Li K. BRIT1/MCPH1 Is Essential for Mitotic and Meiotic Recombination DNA Repair and Maintaining Genomic Stability in Mice. PLOS Genetics 2010, 6: e1000826. PMID: 20107607, PMCID: PMC2809772, DOI: 10.1371/journal.pgen.1000826.Peer-Reviewed Original ResearchConceptsMouse embryonic fibroblastsDNA double-strand breaksDNA repairGenomic stabilityDNA damage response pathwayBRIT1/MCPH1Meiotic homologous recombinationDNA damage signalingDamage response pathwayRecruitment of RAD51Localization of RAD51Novel key regulatorRAD51 foci formationDouble-strand breaksIrradiation-induced DNA damagePrimary microcephaly patientsBRCT domainMutant spermatocytesBRCA2 complexMCPH1 functionDamage signalingMeiotic chromosomesChromosomal synapsisProphase IResponse pathways
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 lesionsMre1ChromosomesComplexesProteinAlleles
2008
Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis
Cosme-Blanco W, Chang S. Dual roles of telomere dysfunction in initiation and suppression of tumorigenesis. Experimental Cell Research 2008, 314: 1973-1979. PMID: 18448098, PMCID: PMC3690559, DOI: 10.1016/j.yexcr.2008.03.011.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDysfunctional telomeresGenomic instabilityPotent tumor suppressor mechanismTumorigenic potentialSimple repeat sequencesTumor suppressor mechanismDouble-strand breaksCell tumorigenic potentialSuppression of tumorigenesisCancer cellsChromosomal endsTelomere dysfunctionCellular senescenceRepeat sequencesGenetic changesTelomeresGenetic lesionsP53 pathwayTumor initiationDicentric chromosomesSuppressor mechanismIntact p53 pathwayHuman carcinomasRare cells