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
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 ResearchConceptsTelomere 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
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 Proteins
2008
Differential regulation of centrosome integrity by DNA damage response proteins
Rai R, Phadnis A, Haralkar S, Badwe RA, Dai H, Li K, Lin SY. Differential regulation of centrosome integrity by DNA damage response proteins. Cell Cycle 2008, 7: 2225-2233. PMID: 18635967, PMCID: PMC2557875, DOI: 10.4161/cc.7.14.6303.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAurora KinasesBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCentrosomeCytokinesisCytoskeletal ProteinsDisease ProgressionDNA DamageFemaleHumansMitosisModels, BiologicalNerve Tissue ProteinsNuclear ProteinsProtein Serine-Threonine KinasesProtein TransportProto-Oncogene ProteinsSpindle ApparatusTrans-ActivatorsConceptsCentrosome integritySpindle assemblyCentrosome duplicationDNA damage response proteinsProper centrosome duplicationDamage response proteinsMitotic spindle assemblySpindle checkpoint activationTumor suppressor geneDefective mitosisChromosome missegregationCentrosomal kinaseDefective cytokinesisCheckpoint activationCentrosome maturationNovel functionResponse proteinsBRIT1MDC1Key regulatorNegative regulatorAurora ACentrosome overduplicationDifferential regulationDNA damage
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 moleculesBRIT1 regulates early DNA damage response, chromosomal integrity, and cancer
Rai R, Dai H, Multani AS, Li K, Chin K, Gray J, Lahad JP, Liang J, Mills GB, Meric-Bernstam F, Lin SY. BRIT1 regulates early DNA damage response, chromosomal integrity, and cancer. Cancer Cell 2006, 10: 145-157. PMID: 16872911, PMCID: PMC1557410, DOI: 10.1016/j.ccr.2006.07.002.Peer-Reviewed Original ResearchMeSH KeywordsBase SequenceBreast NeoplasmsCell Cycle ProteinsCell Line, TumorCell NucleusCell Transformation, NeoplasticChromatinChromosome AberrationsCytoskeletal ProteinsDNA DamageFemaleGene DosageHumansMolecular Sequence DataMutationNerve Tissue ProteinsNuclear ProteinsOvarian NeoplasmsTrans-ActivatorsTumor Suppressor ProteinsConceptsATM/ATR pathwayDNA damage response pathwayEarly DNA damage responseDNA damage regulatorDNA damage checkpointDamage response pathwayDNA damage responseTumor suppressor geneHTERT repressorDamage checkpointATR pathwayDamage responseResponse pathwaysBRIT1Chromosomal integrityGenomic instabilitySuppressor geneHuman cancersAdditional functionsChromosomal aberrationsPathwayMDC1NBS1RepressorGenes
2005
BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1–Chk1 pathway, implicating checkpoint dysfunction in microcephaly
Lin SY, Rai R, Li K, Xu ZX, Elledge SJ. BRIT1/MCPH1 is a DNA damage responsive protein that regulates the Brca1–Chk1 pathway, implicating checkpoint dysfunction in microcephaly. Proceedings Of The National Academy Of Sciences Of The United States Of America 2005, 102: 15105-15109. PMID: 16217032, PMCID: PMC1257745, DOI: 10.1073/pnas.0507722102.Peer-Reviewed Original ResearchConceptsDNA damage responsive proteinBRIT1/MCPH1Human telomerase functionDamage-responsive proteinsChromatin-associated proteinsPhosphorylation of Nbs1Checkpoint kinase Chk1G2/M checkpointSeckel syndrome patientsCell cycle arrestGamma-H2AX fociKinase Chk1Nuclear fociResponsive proteinsTelomerase functionMicrocephaly disordersMCPH1 geneCellular immortalizationBRIT1MCPH1 deficiencyChk1 pathwayAtaxia telangiectasiaM checkpointPrimary microcephalyChk1