2020
Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly
Cicconi A, Rai R, Xiong X, Broton C, Al-Hiyasat A, Hu C, Dong S, Sun W, Garbarino J, Bindra RS, Schildkraut C, Chen Y, Chang S. Microcephalin 1/BRIT1-TRF2 interaction promotes telomere replication and repair, linking telomere dysfunction to primary microcephaly. Nature Communications 2020, 11: 5861. PMID: 33203878, PMCID: PMC7672075, DOI: 10.1038/s41467-020-19674-0.Peer-Reviewed Original ResearchAminopeptidasesAnimalsBinding SitesCalorimetryCell Cycle ProteinsCytoskeletal ProteinsDipeptidyl-Peptidases and Tripeptidyl-PeptidasesDNA DamageFibroblastsHeLa CellsHistonesHumansMiceMicrocephalyMutationProtein Interaction Domains and MotifsSerine ProteasesShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2
2019
The Replisome Mediates A-NHEJ Repair of Telomeres Lacking POT1-TPP1 Independently of MRN Function
Rai R, Gu P, Broton C, Kumar-Sinha C, Chen Y, Chang S. The Replisome Mediates A-NHEJ Repair of Telomeres Lacking POT1-TPP1 Independently of MRN Function. Cell Reports 2019, 29: 3708-3725.e5. PMID: 31825846, PMCID: PMC7001145, DOI: 10.1016/j.celrep.2019.11.012.Peer-Reviewed Original ResearchMeSH KeywordsAcid Anhydride HydrolasesAdaptor Proteins, Signal TransducingAminopeptidasesAnimalsCell Cycle ProteinsCell Line, TumorCells, CulturedCheckpoint Kinase 1Dipeptidyl-Peptidases and Tripeptidyl-PeptidasesDNA End-Joining RepairDNA Repair EnzymesDNA-Binding ProteinsDNA-Directed DNA PolymeraseExodeoxyribonucleasesHEK293 CellsHumansMiceMRE11 Homologue ProteinMultienzyme ComplexesProliferating Cell Nuclear AntigenSerine ProteasesShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2ConceptsReplication protein AReplisome complexPOT1-TPP1Dysfunctional telomeresDNA damage sensor MRE11-RAD50DNA damage checkpoint responseAlternative non-homologous endNon-homologous endMRN functionChromosome endsMre11-Rad50Checkpoint responseDNA-PKTelomeric overhangMre11 nucleaseTelomere repairEnd resectionRAD-51Repair pathwaysAtaxia telangiectasiaTelomeresC-strandDNA damageReplisomeClaspin
2017
Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex
Hu C, Rai R, Huang C, Broton C, Long J, Xu Y, Xue J, Lei M, Chang S, Chen Y. Structural and functional analyses of the mammalian TIN2-TPP1-TRF2 telomeric complex. Cell Research 2017, 27: 1485-1502. PMID: 29160297, PMCID: PMC5717407, DOI: 10.1038/cr.2017.144.Peer-Reviewed Original ResearchConceptsShelterin complexTelomeric DNAStructure-based mutagenesis analysisProtein-protein interaction platformRepetitive DNA sequencesTelomere end protectionN-terminal domainMammalian telomeresChromosome endsTelomeric complexNucleoprotein complexesMutagenesis analysisEnd protectionDNA sequencesLike domainHeterodimer bindsTIN2Functional analysisMolecular mechanismsTRF2TPP1Stable assemblyEssential roleTRF1TelomeresStructural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer
Chen C, Gu P, Wu J, Chen X, Niu S, Sun H, Wu L, Li N, Peng J, Shi S, Fan C, Huang M, Wong CC, Gong Q, Kumar-Sinha C, Zhang R, Pusztai L, Rai R, Chang S, Lei M. Structural insights into POT1-TPP1 interaction and POT1 C-terminal mutations in human cancer. Nature Communications 2017, 8: 14929. PMID: 28393832, PMCID: PMC5394241, DOI: 10.1038/ncomms14929.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsConserved SequenceDNA DamageDNA Mutational AnalysisDNA RepairGenomic InstabilityHumansMiceModels, MolecularMolecular ChaperonesMutationNeoplasmsPhosphoproteinsProstaglandin-E SynthasesProtein BindingProtein Structure, SecondaryScattering, Small AngleShelterin ComplexStructure-Activity RelationshipTelomere-Binding ProteinsX-Ray DiffractionConceptsTelomerase-mediated telomere extensionHuman cancersDNA damage responseC-terminal mutationsOB foldsHuman POT1Chromosome endsGenome instabilityPOT1-TPP1Telomere extensionDamage responseStable heterodimerA-NHEJStructural insightsC-terminusInappropriate repairTPP1POT1Heart-shaped structureMissense mutationsTerminal portionMutationsDomainMutantsTelomeresCytogenetic Analysis of Telomere Dysfunction
Rai R, Multani AS, Chang S. Cytogenetic Analysis of Telomere Dysfunction. Methods In Molecular Biology 2017, 1587: 127-131. PMID: 28324504, DOI: 10.1007/978-1-4939-6892-3_12.Peer-Reviewed Original ResearchProbing 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 ResearchConceptsTelomere dysfunctionDNA damage response signalsDNA damage repair pathwaysTelomere damage responseΓ-H2AXDamage repair pathwaysCheckpoint sensorNbs1 complexReplicative attritionMre11-Rad50Shelterin componentsDamage responseTelomeric DNADysfunctional telomeresRepair pathwaysDownstream effectorsComplete deletionTelomeresDNAPathwayTRF2Chk2Chk1KinaseEffectors
2016
TRF2-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
2011
The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection
Rai R, Li JM, Zheng H, Lok GT, Deng Y, Huen MS, Chen J, Jin J, Chang S. The E3 ubiquitin ligase Rnf8 stabilizes Tpp1 to promote telomere end protection. Nature Structural & Molecular Biology 2011, 18: 1400-1407. PMID: 22101936, PMCID: PMC3657743, DOI: 10.1038/nsmb.2172.Peer-Reviewed Original ResearchProbing the Telomere Damage Response
Rai R, Chang S. Probing the Telomere Damage Response. Methods In Molecular Biology 2011, 735: 145-150. PMID: 21461819, PMCID: PMC3690558, DOI: 10.1007/978-1-61779-092-8_14.Peer-Reviewed Original ResearchConceptsTelomere dysfunctionDNA damage response signalsDNA damage repair pathwaysTelomere damage responseΓ-H2AXDamage repair pathwaysCheckpoint sensorNbs1 complexReplicative attritionMre11-Rad50Shelterin componentsDamage responseTelomeric DNADysfunctional telomeresRepair pathwaysDownstream effectorsComplete deletionTelomeresDNAPathwayTRF2Chk2Chk1KinaseEffectorsA conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms
Chen Y, Rai R, Zhou ZR, Kanoh J, Ribeyre C, Yang Y, Zheng H, Damay P, Wang F, Tsujii H, Hiraoka Y, Shore D, Hu HY, Chang S, Lei M. A conserved motif within RAP1 has diversified roles in telomere protection and regulation in different organisms. Nature Structural & Molecular Biology 2011, 18: 213-221. PMID: 21217703, PMCID: PMC3688267, DOI: 10.1038/nsmb.1974.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsCells, CulturedCrystallography, X-RayFungal ProteinsHeLa CellsHumansModels, MolecularMolecular Sequence DataMutationNuclear Magnetic Resonance, BiomolecularProtein BindingProtein Interaction Domains and MotifsSaccharomycetalesSchizosaccharomycesShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2ConceptsRap1 C-terminusDifferent interacting partnersProtein Rap1Fission yeastTelomere protectionInteracting partnerTranscriptional silencingDifferent organismsC-terminusFunctional analysisInteraction moduleYeastRap1Different functionsOrganismsTaz1Sir3TRF2MammalianTelomeresSilencingMammalsMotifCrystal structureRegulation
2010
The function of classical and alternative non‐homologous end‐joining pathways in the fusion of dysfunctional telomeres
Rai R, Zheng H, He H, Luo Y, Multani A, Carpenter PB, Chang S. The function of classical and alternative non‐homologous end‐joining pathways in the fusion of dysfunctional telomeres. The EMBO Journal 2010, 29: 2598-2610. PMID: 20588252, PMCID: PMC2928694, DOI: 10.1038/emboj.2010.142.Peer-Reviewed Original ResearchAnimalsAntigens, NuclearCells, CulturedChromosomal Proteins, Non-HistoneDNA RepairDNA-Binding ProteinsHumansIntracellular Signaling Peptides and ProteinsKu AutoantigenMiceMice, KnockoutShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2Tumor Suppressor p53-Binding Protein 1
2007
DNA damage response: the players, the network and the role in tumor suppression.
Rai R, Peng G, Li K, Lin SY. DNA damage response: the players, the network and the role in tumor suppression. Cancer Genomics & Proteomics 2007, 4: 99-106. PMID: 17804872.Peer-Reviewed Original ResearchConceptsDNA damage responseDamage responseDNA-damaging insultsCell cycle checkpointsDNA damage lesionsGenomic integrityCycle checkpointsDNA repairGenomic instabilityTumor suppressionMolecular eventsGenetic instabilityDNA damageDamage lesionsCancer developmentNormal cellsComplex mechanismsCommon featureCheckpointTumorigenesisPathwayResponseCells
2006
BRIT1/MCPH1: A Guardian of Genome and an Enemy of Tumors
Chaplet M, Rai R, Jackson-Bernitsas D, Li K, Lin SY. BRIT1/MCPH1: A Guardian of Genome and an Enemy of Tumors. Cell Cycle 2006, 5: 2579-2583. PMID: 17172830, DOI: 10.4161/cc.5.22.3471.Peer-Reviewed Original ResearchConceptsDNA damageTiming of mitosisDNA damage checkpointDNA damage responseCell cycle checkpointsGuardian of genomePotential tumor suppressorDamage checkpointEukaryotic cellsIntriguing proteinNuclear fociGenomic stabilityDamage responseCycle checkpointsBRIT1Damage sensorTumor suppressorCellular responsesSophisticated mechanismsCancer initiationCentrosomal abnormalitiesNeoplastic transformationGenomeProteinImportant molecules