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
2017
Structural 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 portionMutationsDomainMutantsTelomeresProbing 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
2015
Monitoring the DNA Damage Response at Dysfunctional Telomeres
Rai R, Chang S. Monitoring the DNA Damage Response at Dysfunctional Telomeres. Methods In Molecular Biology 2015, 1343: 175-180. PMID: 26420717, DOI: 10.1007/978-1-4939-2963-4_14.Peer-Reviewed Original ResearchConceptsDysfunctional telomeresDNA damage sensorDNA damage responseDNA damage fociSitu hybridization approachEukaryotic chromosomesShelterin componentsDNA repeatsGenomic stabilityDDR proteinsDamage responseTelomeric DNADDR pathwaysDamage fociChromosomal endsTelomere dysfunctionDamage sensorTelomeresDNA damageHybridization approachCellular viabilityPathwayProper maintenanceChromosomesRepeats
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 deletionTelomeresDNAPathwayTRF2Chk2Chk1KinaseEffectors
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
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 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