2021
Distinct functions of POT1 proteins contribute to the regulation of telomerase recruitment to telomeres
Gu P, Jia S, Takasugi T, Tesmer VM, Nandakumar J, Chen Y, Chang S. Distinct functions of POT1 proteins contribute to the regulation of telomerase recruitment to telomeres. Nature Communications 2021, 12: 5514. PMID: 34535663, PMCID: PMC8448735, DOI: 10.1038/s41467-021-25799-7.Peer-Reviewed Original ResearchConceptsDNA damage responseTelomerase recruitmentPOT1 proteinsDamage responseATR-dependent DNA damage responseNon-homologous end-joining DNA repair pathwayRecruitment of telomeraseC-strand fillAmino acidsDNA repair pathwaysUnique amino acidsTEN1 (CST) complexTelomere extensionCTC1-STN1Stable heterodimerRepair pathwaysC-terminusDistinct functionsPOT1bPOT1aTelomeresC-strandG-strandTPP1Protein
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 portionMutationsDomainMutantsTelomeres
2013
Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus
Gu P, Chang S. Functional characterization of human CTC1 mutations reveals novel mechanisms responsible for the pathogenesis of the telomere disease Coats plus. Aging Cell 2013, 12: 1100-1109. PMID: 23869908, PMCID: PMC4083614, DOI: 10.1111/acel.12139.Peer-Reviewed Original ResearchConceptsCTC1 mutationsFrameshift mutantsTelomere dysfunctionUnstable protein productsDNA/protein structuresFirst biochemical characterizationDNA PolαStn1-Ten1CST complexFused chromosomeGenome stabilityTelomere functionTelomere replicationMissense mutantsCTC1-STN1Functional characterizationBiochemical characterizationProtein productsProtein structureRare recessive disorderTelomeresMutantsMissense mutationsNovel mechanismFrameshift mutationSingle strand DNA binding proteins 1 and 2 protect newly replicated telomeres
Gu P, Deng W, Lei M, Chang S. Single strand DNA binding proteins 1 and 2 protect newly replicated telomeres. Cell Research 2013, 23: 705-719. PMID: 23459151, PMCID: PMC3641597, DOI: 10.1038/cr.2013.31.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsCell LineChromatidsDNA DamageDNA RepairDNA, Single-StrandedDNA-Binding ProteinsGenomic InstabilityHumansMiceMice, KnockoutMitochondrial ProteinsProtein BindingRadiation, IonizingRNA InterferenceRNA, Small InterferingShelterin ComplexTelomereTelomere-Binding ProteinsTelomeric Repeat Binding Protein 2ConceptsGenome stabilitySingle-strand DNAHeterotrimeric protein complexDNA damage responseTelomere end protectionProtein 1Subset of telomeresTelomeric ssDNAProtein complexesTelomeric DNADamage responseG-overhangsEnd protectionConditional knockout miceTelomeresΔ miceDNAPOT1aDevelopmental abnormalitiesStrand DNACritical roleKnockout miceINTS3F allelePOT1b
2011
Differential Recruitment of Methyl CpG‐Binding Domain Factors and DNA Methyltransferases by the Orphan Receptor Germ Cell Nuclear Factor Initiates the Repression and Silencing of Oct4
Gu P, Xu X, Le Menuet D, Chung A, Cooney AJ. Differential Recruitment of Methyl CpG‐Binding Domain Factors and DNA Methyltransferases by the Orphan Receptor Germ Cell Nuclear Factor Initiates the Repression and Silencing of Oct4. Stem Cells 2011, 29: 1041-1051. PMID: 21608077, PMCID: PMC3468724, DOI: 10.1002/stem.652.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsCell DifferentiationCell Line, TumorCpG IslandsDNA (Cytosine-5-)-MethyltransferasesDNA MethylationDNA Methyltransferase 3ADNA-Binding ProteinsEmbryonic Stem CellsGene Expression Regulation, DevelopmentalGene Knockdown TechniquesMiceMolecular Sequence DataNuclear Receptor Subfamily 6, Group A, Member 1Octamer Transcription Factor-3Promoter Regions, GeneticProtein BindingTranscription FactorsConceptsGerm cell nuclear factorEmbryonic stem cellsOct4 promoterDNA methylationDNA methyltransferasesRepressive functionEpigenetic modificationsTranscription factorsProximal promoterDifferentiation of ESCsWild-type embryonic stem cellsDe novo DnmtsGene-specific repressionKey transcription factorDifferential recruitmentNuclear factorGCNF bindsESC differentiationPluripotency genesOct4 geneSomatic cellsMethyl-CpGCis elementsMBD3Gene expression
2005
Orphan Nuclear Receptor GCNF Is Required for the Repression of Pluripotency Genes during Retinoic Acid-Induced Embryonic Stem Cell Differentiation
Gu P, LeMenuet D, Chung A, Mancini M, Wheeler DA, Cooney AJ. Orphan Nuclear Receptor GCNF Is Required for the Repression of Pluripotency Genes during Retinoic Acid-Induced Embryonic Stem Cell Differentiation. Molecular And Cellular Biology 2005, 25: 8507-8519. PMID: 16166633, PMCID: PMC1265758, DOI: 10.1128/mcb.25.19.8507-8519.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, NorthernBlotting, WesternCell DifferentiationCell LineCell NucleusChromatin ImmunoprecipitationDNA-Binding ProteinsDown-RegulationEmbryo, MammalianFemaleFibroblast Growth Factor 4GenotypeHomeodomain ProteinsIn Situ HybridizationMaleMiceMice, TransgenicMicroscopy, FluorescenceModels, GeneticNanog Homeobox ProteinNuclear Receptor Subfamily 6, Group A, Member 1Octamer Transcription Factor-3PhenotypePlasmidsProtein BindingReceptors, Cytoplasmic and NuclearResponse ElementsReverse Transcriptase Polymerase Chain ReactionSignal TransductionSOXB1 Transcription FactorsStem CellsTime FactorsTrans-ActivatorsTransfectionTretinoinConceptsLoss of repressionES cell differentiationPluripotency genesCell differentiationTranscription factorsEmbryonic developmentES cellsEmbryonic stem cell pluripotencyEmbryonic stem cell differentiationEarly mouse embryonic developmentStem cell pluripotencyMouse embryonic developmentPluripotency gene expressionEarly embryonic developmentInitiation of differentiationStem cell differentiationRetinoic acidCell pluripotencyNanog geneGenes Oct4Somatic cellsUndifferentiated stateGene expressionGCNFRepressionCorrelated Evolutionary Pressure at Interacting Transcription Factors and DNA Response Elements Can Guide the Rational Engineering of DNA Binding Specificity
Raviscioni M, Gu P, Sattar M, Cooney AJ, Lichtarge O. Correlated Evolutionary Pressure at Interacting Transcription Factors and DNA Response Elements Can Guide the Rational Engineering of DNA Binding Specificity. Journal Of Molecular Biology 2005, 350: 402-415. PMID: 15946684, DOI: 10.1016/j.jmb.2005.04.054.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiological EvolutionComputational BiologyDNADNA Mutational AnalysisDNA-Binding ProteinsEntropyEvolution, MolecularGenomicsHumansModels, GeneticModels, StatisticalMutationNucleic Acid ConformationPhylogenyProtein BindingProtein EngineeringReceptors, Cytoplasmic and NuclearReceptors, EstrogenResponse ElementsSoftwareThermodynamicsTranscription FactorsConceptsDNA binding specificityTranscription factorsBinding specificityEvolutionary importanceEvolutionary pressureResponse elementInteracting Transcription FactorsRational engineeringRelative evolutionary importanceProtein-DNA interfaceProtein-DNA interactionsTranscription factor proteinsDNA response elementsAmino acid residuesNuclear hormone receptorsTranscriptional regulatorsEvolutionary traceImportant residuesGene expressionRecognition codeMolecular mechanismsAcid residuesFactor proteinProtein residuesLRH-1