2001
Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination
Datta H, Glazer P. Intracellular generation of single-stranded DNA for chromosomal triplex formation and induced recombination. Nucleic Acids Research 2001, 29: 5140-5147. PMID: 11812847, PMCID: PMC97609, DOI: 10.1093/nar/29.24.5140.Peer-Reviewed Original ResearchConceptsNovel vector systemMouse cellsInduced recombinationPrimer extension analysisVector systemGenome modificationTriplex formationExtension analysisIntrachromosomal recombinationChromosomal eventsGene expressionSequence insertReporter substrateSuch oligodeoxyribonucleotidesTarget siteSsDNA moleculesIntracellular generationDNARecombinationEfficient intracellular deliveryCellsSuch moleculesSequenceIntracellular deliveryOligodeoxyribonucleotidesChromosome Targeting at Short Polypurine Sites by Cationic Triplex-forming Oligonucleotides*
Vasquez K, Dagle J, Weeks D, Glazer P. Chromosome Targeting at Short Polypurine Sites by Cationic Triplex-forming Oligonucleotides*. Journal Of Biological Chemistry 2001, 276: 38536-38541. PMID: 11504712, DOI: 10.1074/jbc.m101797200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCationsChromosomesCOS CellsDiaminesDNADNA Mutational AnalysisDose-Response Relationship, DrugEthylenediaminesFicusinGenes, ReporterGenes, SuppressorGenetic TechniquesGenomeIndicators and ReagentsMagnesiumMiceMice, KnockoutModels, GeneticMolecular Sequence DataMutagenesisMutagenesis, Site-DirectedNucleic Acid ConformationPotassiumProtein BindingPurinesRNA, TransferSequence Homology, Nucleic AcidConceptsChromosomal reporter geneMonkey COS cellsTarget siteSite-specific mutationsTriplex target sitesChromosome targetingEpisomal targetChromosomal targetsGene mutagenesisMammalian cellsSite-specific inductionChromosomal lociReporter geneCOS cellsGene knockoutGenomic DNAMouse cellsSite-directed modificationOligonucleotide bindsPhosphodiester bondShort sitesThird strand bindingPhosphodiester backboneSystemic administrationDNADirected gene modification via triple helix formation.
Gorman L, Glazer P. Directed gene modification via triple helix formation. 2001, 1: 391-9. PMID: 11899085, DOI: 10.2174/1566524013363771.Peer-Reviewed Original ResearchConceptsGene modificationNon-functional gene productMammalian genesGene productsGenomic DNASingle nucleotideDefective geneTriple helix formationGenetic diseasesTriplex formingGenesHelix formationEfficient targetingNucleic acidsDNAInitial stepGene therapyCorrect sequenceNucleotidesMutationsMoleculesImportant advancesSequenceTargetingModificationHypermutability to ionizing radiation in mismatch repair-deficient, Pms2 knockout mice.
Xu X, Narayanan L, Dunklee B, Liskay R, Glazer P. Hypermutability to ionizing radiation in mismatch repair-deficient, Pms2 knockout mice. Cancer Research 2001, 61: 3775-80. PMID: 11325851.Peer-Reviewed Original ResearchConceptsMismatch repairSimple sequence repeatsWild-type transgenic miceCell linesLambda cII geneMutation frequencyDNA mismatch repairHigher clonogenic survivalMMR-deficient miceLambda shuttle vectorTolerance phenotypeSequence repeatsPatterns of IRReporter geneRepeat sequencesMononucleotide repeat sequencesShuttle vectorSingle bp deletionCII geneNullizygous animalsNullizygous miceHypermutabilityBp deletionWild-type miceClonogenic survival
2000
Specific Mutations Induced by Triplex-Forming Oligonucleotides in Mice
Vasquez K, Narayanan L, Glazer P. Specific Mutations Induced by Triplex-Forming Oligonucleotides in Mice. Science 2000, 290: 530-533. PMID: 11039937, DOI: 10.1126/science.290.5491.530.Peer-Reviewed Original ResearchConceptsSomatic cellsSpecific genomic sitesEmbryonic stem cell technologyDuplex DNA sequencesGene functionGreater mutation frequenciesGenomic sitesGenome modificationChromosomal copyDNA sequencesSequence-controlled oligomersReporter geneStem cell technologyControl genesGerm-line mutationsGenesSpecific mutationsSupF geneControl oligomersMutationsMutation frequencyTransgenic miceOligonucleotideCellsMutation detectionHigh-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells
Luo Z, Macris M, Faruqi A, Glazer P. High-frequency intrachromosomal gene conversion induced by triplex-forming oligonucleotides microinjected into mouse cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 9003-9008. PMID: 10900269, PMCID: PMC16811, DOI: 10.1073/pnas.160004997.Peer-Reviewed Original ResearchConceptsTriple helix-forming oligonucleotidesLtk- cell lineTK geneChromosomal lociIntrachromosomal gene conversionMouse Ltk- cell lineSingle chromosomal locusFunctional tk geneGene conversion eventsSite-specific recombinationSequence-specific mannerCell linesSimplex virus thymidine kinase geneVirus thymidine kinase geneHerpes simplex virus thymidine kinase geneThymidine kinase geneGene conversionIdentical base compositionMammalian cellsDownstream genesConversion eventsChromosomal sitesBase compositionKinase geneMutant copiesTriple-Helix Formation Induces Recombination in Mammalian Cells via a Nucleotide Excision Repair-Dependent Pathway
Faruqi A, Datta H, Carroll D, Seidman M, Glazer P. Triple-Helix Formation Induces Recombination in Mammalian Cells via a Nucleotide Excision Repair-Dependent Pathway. Molecular And Cellular Biology 2000, 20: 990-1000. PMID: 10629056, PMCID: PMC85216, DOI: 10.1128/mcb.20.3.990-1000.2000.Peer-Reviewed Original ResearchAnimalsBase SequenceCell Line, TransformedChromosome MappingColonic NeoplasmsCOS CellsDNA RepairDNA-Binding ProteinsGenes, ReporterGenes, SuppressorHumansModels, GeneticMutagenesisNucleic Acid ConformationOligodeoxyribonucleotidesRecombinant ProteinsRecombination, GeneticRNA, TransferRNA-Binding ProteinsSequence DeletionTransfectionTumor Cells, CulturedXeroderma Pigmentosum Group A ProteinActivation of human γ-globin gene expression via triplex-forming oligonucleotide (TFO)-directed mutations in the γ-globin gene 5′ flanking region
Xu X, Glazer P, Wang G. Activation of human γ-globin gene expression via triplex-forming oligonucleotide (TFO)-directed mutations in the γ-globin gene 5′ flanking region. Gene 2000, 242: 219-228. PMID: 10721715, DOI: 10.1016/s0378-1119(99)00522-3.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesCell LineDNADNA-Binding ProteinsGene Expression RegulationGlobinsHeLa CellsHost Cell Factor C1HumansK562 CellsMolecular Sequence DataMutagenesis, Site-DirectedMutationOctamer Transcription Factor-1OligonucleotidesProtein BindingRegulatory Sequences, Nucleic AcidTranscription FactorsTumor Cells, CulturedConceptsGamma-globin gene expressionGamma-globin geneGene expressionHuman γ-globin gene expressionVivo gene expression assaysΓ-globin gene expressionGenetic diseasesAgamma-globin geneMouse erythroleukemia cellsTarget gene expressionTarget siteBeta-globin disordersFetal hemoglobin (HPFH) conditionBeta-globin geneSingle base changeGene expression assaysProtein binding assaysTranscription factorsHuman normal fibroblast cellsDNA sequencing analysisCommon genetic diseaseFlanking regionsExpression assaysErythroleukemia cellsTriplex-forming oligonucleotides
1999
The Tyr-265-to-Cys mutator mutant of DNA polymerase β induces a mutator phenotype in mouse LN12 cells
Clairmont C, Narayanan L, Sun K, Glazer P, Sweasy J. The Tyr-265-to-Cys mutator mutant of DNA polymerase β induces a mutator phenotype in mouse LN12 cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 9580-9585. PMID: 10449735, PMCID: PMC22251, DOI: 10.1073/pnas.96.17.9580.Peer-Reviewed Original ResearchConceptsMutator mutantsDNA polymerase betaTyr-265Mutator phenotypePolymerase betaWild-type DNA polymerase betaWild-type DNA polymeraseWild-type proteinBase excision repairRat DNA polymerase betaSpontaneous mutation frequencyDNA polymerase βDNA polymerase IMammalian cellsMutator polymeraseComplementation systemBeta mutantsExcision repairPolymerase IMutantsMutator activityGenetic instabilityHuman cellsPolymerase βEscherichia coliPeptide nucleic acid (PNA) binding-mediated induction of human γ-globin gene expression
Wang G, Xu X, Pace B, Dean D, Glazer P, Chan P, Goodman S, Shokolenko I. Peptide nucleic acid (PNA) binding-mediated induction of human γ-globin gene expression. Nucleic Acids Research 1999, 27: 2806-2813. PMID: 10373600, PMCID: PMC148492, DOI: 10.1093/nar/27.13.2806.Peer-Reviewed Original ResearchConceptsGamma-globin gene expressionGamma-globin geneD-loop structureGene expressionHuman γ-globin gene expressionΓ-globin gene expressionGenetic diseasesK562 human erythroleukemia cellsGene expression strategyReporter gene constructsSequence-specific mannerBeta-globin geneHuman erythroleukemia cellsInduction of expressionAdult blood cellsEndogenous genesCommon genetic diseaseGene productsGene constructsExpression strategyErythroleukemia cellsHomopurine/homopyrimidine sequencesHuman diseasesGenesGlobin disordersTargeted Correction of an Episomal Gene in Mammalian Cells by a Short DNA Fragment Tethered to a Triplex-forming Oligonucleotide*
Chan P, Lin M, Faruqi A, Powell J, Seidman M, Glazer P. Targeted Correction of an Episomal Gene in Mammalian Cells by a Short DNA Fragment Tethered to a Triplex-forming Oligonucleotide*. Journal Of Biological Chemistry 1999, 274: 11541-11548. PMID: 10206960, DOI: 10.1074/jbc.274.17.11541.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCell LineCOS CellsDNADNA RepairHumansIndicators and ReagentsPlasmidsPoint MutationConceptsMammalian cellsGene correctionSV40 shuttle vectorTriplex motifNucleotide excision repairSequence-specific mannerEpisomal geneSupF reporter geneXPA cDNASpecific target sitesGene conversionShort DNA fragmentsDNA repairGene targetingTarget genesDNA segmentsReporter geneExcision repairDNA fragmentsBifunctional oligonucleotidesShuttle vectorSequence conversionGenesSV40 vectorsFlexible linkerChromosomal mutations induced by triplex-forming oligonucleotides in mammalian cells
Vasquez K, Wang G, Havre P, Glazer P. Chromosomal mutations induced by triplex-forming oligonucleotides in mammalian cells. Nucleic Acids Research 1999, 27: 1176-1181. PMID: 9927753, PMCID: PMC148300, DOI: 10.1093/nar/27.4.1176.Peer-Reviewed Original ResearchConceptsTriplex-forming oligonucleotidesMutation reporter geneMultiple chromosomal copiesMutation frequencyMammalian chromosomesTriplex binding siteMammalian cellsChromosomal copyFibroblast cell lineChromosomal lociGenetic manipulationMouse fibroblast cell lineSequencing dataChromosomal mutationsDuplex DNAUntreated control cellsBinding sitesCell linesControl cellsSpecific recognitionMutagenesisMutationsT transversionSpecific sitesCellsTriplex Formation by Oligonucleotides Containing 5-(1-Propynyl)-2‘-deoxyuridine: Decreased Magnesium Dependence and Improved Intracellular Gene Targeting †
Lacroix L, Lacoste J, Reddoch J, Mergny J, Levy D, Seidman M, Matteucci M, Glazer P. Triplex Formation by Oligonucleotides Containing 5-(1-Propynyl)-2‘-deoxyuridine: Decreased Magnesium Dependence and Improved Intracellular Gene Targeting †. Biochemistry 1999, 38: 1893-1901. PMID: 10026270, DOI: 10.1021/bi982290q.Peer-Reviewed Original Research
1998
Targeted gene knockout mediated by triple helix forming oligonucleotides
Majumdar A, Khorlin A, Dyatkina N, Lin F, Powell J, Liu J, Fei Z, Khripine Y, Watanabe K, George J, Glazer P, Seidman M. Targeted gene knockout mediated by triple helix forming oligonucleotides. Nature Genetics 1998, 20: 212-214. PMID: 9771719, DOI: 10.1038/2530.Peer-Reviewed Original Research
1997
Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2
Narayanan L, Fritzell J, Baker S, Liskay R, Glazer P. Elevated levels of mutation in multiple tissues of mice deficient in the DNA mismatch repair gene Pms2. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 3122-3127. PMID: 9096356, PMCID: PMC20332, DOI: 10.1073/pnas.94.7.3122.Peer-Reviewed Original ResearchConceptsDNA mismatch repair gene PMS2Multiple tissuesMutation reporter geneMismatch repair gene PMS2Role of mutagenesisMammalian homologGenomic integrityReporter geneRepeat sequencesPMS2 locusMononucleotide repeat sequencesGenetic instabilityLimited tissue distributionDNA mismatch repair genesRepair genesHereditary colon cancerNormal developmentSlippage errorsGenesMutagenic treatmentEssential roleMismatch repair genesMutagenesisMutation frequencyHybrid transgenic mice
1996
Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant.
Raha M, Wang G, Seidman M, Glazer P. Mutagenesis by third-strand-directed psoralen adducts in repair-deficient human cells: high frequency and altered spectrum in a xeroderma pigmentosum variant. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 2941-2946. PMID: 8610147, PMCID: PMC39739, DOI: 10.1073/pnas.93.7.2941.Peer-Reviewed Original ResearchRecA protein-mediated irreversible fixation of an oligodeoxyribonucleotide to specific site in DNA
Golub E, Glazer P, Ward D, Radding C. RecA protein-mediated irreversible fixation of an oligodeoxyribonucleotide to specific site in DNA. Mutation Research/Fundamental And Molecular Mechanisms Of Mutagenesis 1996, 351: 117-124. PMID: 8622705, DOI: 10.1016/0027-5107(95)00212-x.Peer-Reviewed Original ResearchMutagenesis in Mammalian Cells Induced by Triple Helix Formation and Transcription-Coupled Repair
Wang G, Seidman M, Glazer P. Mutagenesis in Mammalian Cells Induced by Triple Helix Formation and Transcription-Coupled Repair. Science 1996, 271: 802-805. PMID: 8628995, DOI: 10.1126/science.271.5250.802.Peer-Reviewed Original ResearchConceptsMammalian cellsSufficient binding affinitiesTranscription-coupled repairHuman cell extractsInhibition of transcriptionSimian virus 40 vectorXeroderma pigmentosum groupExcision repairGenetic instabilityTriple helix formationCell extractsTriplex-forming oligonucleotidesGroup B cellsDNA repair synthesisTranscriptionMutagenesisRepair synthesisTriplex DNAHelix formationTriplex formationTriple helixCellsBinding affinitiesTherapeutic applicationsB cellsTriplex‐Mediated, in vitro Targeting of Psoralen Photoadducts within the Genome of a Transgenic Mouse
Gunther E, Havre P, Gasparro F, Glazer P. Triplex‐Mediated, in vitro Targeting of Psoralen Photoadducts within the Genome of a Transgenic Mouse. Photochemistry And Photobiology 1996, 63: 207-212. PMID: 8657733, DOI: 10.1111/j.1751-1097.1996.tb03015.x.Peer-Reviewed Original ResearchConceptsPsoralen modificationMouse DNAGenomic mouse DNAPsoralen photoadductsSequence-specific bindingSequence-specific modificationNucleic acid secondary structureTarget site modificationMammalian genomesAcid secondary structureChromatin structureTriplex binding siteDNA repairTransgenic miceGenomeSequence specificitySecondary structureViral genomeSupF geneDNABinding sitesMutagenesisSite modificationSpecific sitesTriple helixTargeted Mutagenesis Mediated by the Triple Helix Formation
Glazer P, Wang G, Havre P, Gunther E. Targeted Mutagenesis Mediated by the Triple Helix Formation. Methods In Molecular Biology 1996, 57: 109-118. PMID: 8849999, DOI: 10.1385/0-89603-332-5:109.Peer-Reviewed Original Research