2023
Pot1b −/− tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation
Takasugi T, Gu P, Liang F, Staco I, Chang S. Pot1b −/− tumors activate G-quadruplex-induced DNA damage to promote telomere hyper-elongation. Nucleic Acids Research 2023, 51: 9227-9247. PMID: 37560909, PMCID: PMC10516629, DOI: 10.1093/nar/gkad648.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA DamageDNA-Binding ProteinsHumansMiceReplication Protein ASarcomaShelterin ComplexTelomereTelomere-Binding ProteinsConceptsDNA damage responseDamage responseReplication protein A (RPA) complexDependent DNA damage responseTelomere length homeostasisTelomere maintenance mechanismLength homeostasisTelomerase recruitmentPOT1 proteinsHuman POT1Mouse genomeLength maintenanceFunction disruptsReplicative immortalityTelomeresPOT1 mutationsDNA damageHuman cancersLonger telomeresPOT1bMaintenance mechanismsSerial transplantationA complexesSimilar mechanismMutations
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
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
2013
Single 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
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 activity
2008
Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells
Liang J, Wan M, Zhang Y, Gu P, Xin H, Jung SY, Qin J, Wong J, Cooney AJ, Liu D, Songyang Z. Nanog and Oct4 associate with unique transcriptional repression complexes in embryonic stem cells. Nature Cell Biology 2008, 10: 731-739. PMID: 18454139, DOI: 10.1038/ncb1736.Peer-Reviewed Original ResearchConceptsES cell fateRepression complexMouse ES cellsCell fateTranscription factorsES cellsTranscriptional repression complexES cell differentiationEssential transcription factorEmbryonic stem cellsSub-stoichiometric levelsHistone deacetylase activityNuRD complexRepressor complexEndogenous NanogProtein complexesGene transcriptionTarget genesDeacetylase activityNanogNuRDGenesStem cellsCellsComplexes
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-1Evolutionary Trace-based Peptides Identify a Novel Asymmetric Interaction That Mediates Oligomerization in Nuclear Receptors*
Gu P, Morgan DH, Sattar M, Xu X, Wagner R, Raviscioni M, Lichtarge O, Cooney AJ. Evolutionary Trace-based Peptides Identify a Novel Asymmetric Interaction That Mediates Oligomerization in Nuclear Receptors*. Journal Of Biological Chemistry 2005, 280: 31818-31829. PMID: 15994320, DOI: 10.1074/jbc.m501924200.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Vesicular TransportAmino Acid SequenceCell LineDimerizationDNA-Binding ProteinsEvolution, MolecularGenes, ReporterMolecular Sequence DataNuclear Receptor Subfamily 6, Group A, Member 1PeptidesPoint MutationProtein Structure, SecondaryProtein Structure, TertiaryReceptor Cross-TalkReceptors, Cytoplasmic and NuclearReceptors, Retinoic AcidResponse ElementsConceptsGerm cell nuclear factorEvolutionary trace analysisNuclear receptorsKey functional sitesOrphan nuclear receptorDR0 elementsGCNF bindsComplex formationEssential genesEvolutionary traceMolecular basisOligomerization propertiesHelix 3Heterotypic interactionsTargeted mutationsLarge complexesNovel helixFunctional sitesHelix 11HomodimerNuclear factorDimerizationOligomerizationHelixMutationsOrphan Nuclear Receptor LRH-1 Is Required To Maintain Oct4 Expression at the Epiblast Stage of Embryonic Development
Gu P, Goodwin B, Chung A, Xu X, Wheeler DA, Price RR, Galardi C, Peng L, Latour AM, Koller BH, Gossen J, Kliewer SA, Cooney AJ. Orphan Nuclear Receptor LRH-1 Is Required To Maintain Oct4 Expression at the Epiblast Stage of Embryonic Development. Molecular And Cellular Biology 2005, 25: 3492-3505. PMID: 15831456, PMCID: PMC1084298, DOI: 10.1128/mcb.25.9.3492-3505.2005.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlastocystCell DifferentiationDNA-Binding ProteinsDown-RegulationEmbryo, MammalianEmbryonic DevelopmentGene Expression Regulation, DevelopmentalGene SilencingGenes, LethalMiceOctamer Transcription Factor-3Receptors, Cytoplasmic and NuclearResponse ElementsStem CellsTranscription FactorsUp-RegulationConceptsInner cell massEpiblast stageES cellsOct4 expressionOrphan nuclear receptor LRH-1Embryonic developmentLRH-1Proximal enhancerCell lineagesNuclear receptor LRH-1Developmental stagesGerm cell lineagePluripotent cell lineageDifferentiation time pointsEmbryonic stem cellsReporter gene expressionEssential roleUndifferentiated ES cellsCell massSF-1 response elementExpression of Oct4Early developmental stagesOct4 geneDistal enhancerProximal promoter
2003
GCNF‐dependent repression of BMP‐15 and GDF‐9 mediates gamete regulation of female fertility
Lan Z, Gu P, Xu X, Jackson KJ, DeMayo FJ, O'Malley BW, Cooney AJ. GCNF‐dependent repression of BMP‐15 and GDF‐9 mediates gamete regulation of female fertility. The EMBO Journal 2003, 22: 4070-4081. PMID: 12912906, PMCID: PMC175795, DOI: 10.1093/emboj/cdg405.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone Morphogenetic Protein 15Bone Morphogenetic ProteinsCHO CellsCricetinaeDNA-Binding ProteinsEgg ProteinsFemaleFertilityGene Expression RegulationGrowth Differentiation Factor 9IntegrasesIntercellular Signaling Peptides and ProteinsMembrane GlycoproteinsMiceMice, KnockoutMice, TransgenicModels, BiologicalNuclear Receptor Subfamily 6, Group A, Member 1OocytesOvaryReceptors, Cell SurfaceReceptors, Cytoplasmic and NuclearRepressor ProteinsTransforming Growth Factor betaTransgenesViral ProteinsZona PellucidaZona Pellucida GlycoproteinsConceptsGerm cell nuclear factorBMP-15Bone morphogenetic protein 15New regulatory pathwayFemale fertilityGDF-9Growth differentiation factor 9DR0 elementsDifferentiation factor 9Knockout mouse modelSomatic cellsGene promoterRegulatory pathwaysReproductive defectsReporter activityFemale reproductionMolecular studiesFactor 9Paracrine communicationProtein 15Nuclear factorAberrant steroidogenesisExpressionOocytesPrimary defectExpression of the Orphan Nuclear Receptor, Germ Cell Nuclear Factor, in Mouse Gonads and Preimplantation Embryos1
Lan ZJ, Gu P, Xu X, Cooney AJ. Expression of the Orphan Nuclear Receptor, Germ Cell Nuclear Factor, in Mouse Gonads and Preimplantation Embryos1. Biology Of Reproduction 2003, 68: 282-289. PMID: 12493724, DOI: 10.1095/biolreprod.102.008151.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibody SpecificityBase SequenceBlastocystDNADNA-Binding ProteinsFemaleGene Expression Regulation, DevelopmentalImmunohistochemistryIn Vitro TechniquesMaleMiceMice, Inbred C57BLMolecular Sequence DataNuclear Receptor Subfamily 6, Group A, Member 1OocytesOogenesisOvaryPregnancyReceptors, Cytoplasmic and NuclearSpermatogenesisSpermatozoaTestisConceptsGerm cell nuclear factorGCNF proteinMouse gonadsEmbryonic developmentZygotic gene expressionNormal mouse embryonic developmentNuclear receptorsMouse embryonic developmentPreimplantation embryonic developmentSpermatogenic cellsPostmeiotic spermatogenic cellsCytoplasm of oocytesOrphan nuclear receptorNuclear factorPreimplantation Embryos1Early embryosGene transcriptionMaternal proteinsOrphan memberMouse embryosGene expressionPreimplantation embryosGCNFProteinEmbryos