2019
Mitochondrial DNA stress signalling protects the nuclear genome
Wu Z, Oeck S, West AP, Mangalhara KC, Sainz AG, Newman LE, Zhang XO, Wu L, Yan Q, Bosenberg M, Liu Y, Sulkowski PL, Tripple V, Kaech SM, Glazer PM, Shadel GS. Mitochondrial DNA stress signalling protects the nuclear genome. Nature Metabolism 2019, 1: 1209-1218. PMID: 32395698, PMCID: PMC7213273, DOI: 10.1038/s42255-019-0150-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorCell NucleusCytosolDNA DamageDNA, MitochondrialDNA-Binding ProteinsGenomeHigh Mobility Group ProteinsInterferonsInterferon-Stimulated Gene Factor 3Membrane ProteinsMiceMice, KnockoutMice, NudeNF-kappa BNucleotidyltransferasesProtein Serine-Threonine KinasesSignal TransductionConceptsMtDNA stressNuclear DNAGene expressionThousands of copiesMost cell typesRepair responseAcute antiviral responseNuclear genomeCircular mtDNAHigher-order structureInterferon gene expressionEssential proteinsMitochondrial DNACultured primary fibroblastsDNA stressUnphosphorylated formInterferon-stimulated gene expressionMouse melanoma cellsNDNA repairSignaling responseOxidative phosphorylationNDNA damageMtDNA damageMtDNAPrimary fibroblastsCediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51
Kaplan AR, Gueble SE, Liu Y, Oeck S, Kim H, Yun Z, Glazer PM. Cediranib suppresses homology-directed DNA repair through down-regulation of BRCA1/2 and RAD51. Science Translational Medicine 2019, 11 PMID: 31092693, PMCID: PMC6626544, DOI: 10.1126/scitranslmed.aav4508.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBRCA1 ProteinBRCA2 ProteinCell Line, TumorDNA RepairDown-RegulationE2F4 Transcription FactorFemaleGene Expression Regulation, NeoplasticHumansMice, NudePoly(ADP-ribose) Polymerase InhibitorsQuinazolinesRad51 RecombinaseReceptors, Platelet-Derived Growth FactorTumor HypoxiaVascular Endothelial Growth Factor Receptor-2Xenograft Model Antitumor AssaysConceptsHomology-directed DNA repairDNA repairE2F transcription factor 4Protein phosphatase 2ATranscription factor 4DNA repair inhibitorsPhosphatase 2ARAD51 recombinaseTranscriptional corepressorMouse tumor xenograftsSynthetic lethalityGene expressionRB2/Mouse bone marrowGrowth factor receptor inhibitionRepair inhibitorsUnknown mechanismPlatelet-derived growth factor receptor inhibitionFactor 4Human tumorsInhibitor olaparibPARP inhibitorsMutationsCombination of cediranibCancer therapy
2010
Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinoma
Scanlon S, Hegan D, Sulkowski P, Glazer P. Suppression of homology-dependent DNA double-strand break repair induces PARP inhibitor sensitivity in VHL -deficient human renal cell carcinoma. Oncotarget 2010, 5: 2-2. DOI: 10.18632/oncotarget.23445.Peer-Reviewed Original ResearchDouble-strand break repairDNA double-strand break repairBreak repairHomologous recombinationVHL-deficient renal cancer cellsHomology-dependent DNA double-strand break repairGene expressionHuman clear cell renal carcinomaHuman renal cell carcinomaVon Hippel-Lindau (VHL) tumor suppressor geneDNA double-strand breaksDNA repair gene expressionVHL-deficient cellsHr gene expressionRadiation-induced DNA double-strand breaksImpaired DNA double-strand break repairPro-growth stateDouble-strand breaksDNA repair genesRepair gene expressionDNA repair defectsTumor suppressor genePARP inhibitor sensitivityRenal cancer cellsTranscriptional reprogramming
2007
Co-Repression of Mismatch Repair Gene Expression by Hypoxia in Cancer Cells: Role of the Myc/Max Network
Bindra R, Glazer P. Co-Repression of Mismatch Repair Gene Expression by Hypoxia in Cancer Cells: Role of the Myc/Max Network. International Journal Of Radiation Oncology • Biology • Physics 2007, 69: s613. DOI: 10.1016/j.ijrobp.2007.07.1928.Peer-Reviewed Original Research
2006
Peptide Nucleic Acids as Agents to Modify Target Gene Expression and Function
Wang G, Glazer P. Peptide Nucleic Acids as Agents to Modify Target Gene Expression and Function. Medical Intelligence Unit 2006, 223-235. DOI: 10.1007/0-387-32956-0_14.Peer-Reviewed Original ResearchTarget gene expressionGene expressionMolecular mechanismsHuman diseasesGene expression regulationExpression regulationTranscription initiationDNA repairImportant genesMolecular basisTranscriptionGenesNucleic acidsExpressionAbility of PNAMutagenesisAttractive strategyPowerful methodBetter understandingRegulationMechanismPeptide nucleic acidBroad range
2004
Targeted Genome Modification Via Triple Helix Formation
Rogers F, Glazer P. Targeted Genome Modification Via Triple Helix Formation. Cancer Drug Discovery And Development 2004, 27-43. DOI: 10.1007/978-1-59259-777-2_3.Peer-Reviewed Original ResearchDefective geneTargeted genome modificationInhibitors of proteinGene functionGenome modificationGene productsGene expressionTriple helix formationTremendous clinical valueSynthetic oligonucleotidesGenesInherited diseaseHelix formationTreatment of diseasesExpressionDifferent diseasesProteinTherapeutic agentsOligonucleotideTherapeutic useTremendous stridesInhibitorsFunction
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 deliveryOligodeoxyribonucleotidesTriplex forming oligonucleotides: sequence-specific tools for gene targeting
Knauert M, Glazer P. Triplex forming oligonucleotides: sequence-specific tools for gene targeting. Human Molecular Genetics 2001, 10: 2243-2251. PMID: 11673407, DOI: 10.1093/hmg/10.20.2243.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsHuman gene therapyGene therapy agentsAbility of TFOsTriplex formingGenome modificationGene therapyMammalian cellsGenetic manipulationGene targetingGene expressionPotential applicationsGenetic targetingDuplex DNATherapy agentsMajor grooveLoose canonsHigh specificityGenesRecent studiesTargetingRelated moleculesTFOCellsDevicesDNAGenomic Instability in Cancer
Rockwell S, Yuan J, Peretz S, Glazer P. Genomic Instability in Cancer. Novartis Foundation Symposia 2001, 240: 133-151. PMID: 11727926, DOI: 10.1002/0470868716.ch9.Peer-Reviewed Original ResearchConceptsGenomic instabilityChromosomal fragile sitesExposure of cellsNutrient deprivationDNA repairGenomic rearrangementsSelection pressureDNA overreplicationGene expressionGenetic changesFragile sitesGenetic heterogeneityCell proliferationGene amplificationCell populationsBenign cell populationsMutation frequencyHypoxic environmentAggressive phenotypeSolid tumorsExpressionOverreplicationCellsAdverse microenvironmentCytogenetic changes
2000
Activation 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
Peptide 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 disordersTriplex 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 ResearchGenome Modification by Triplex-Forming Oligonucleotides
Vasquez K, Glazer P. Genome Modification by Triplex-Forming Oligonucleotides. Perspectives In Antisense Science 1999, 2: 167-179. DOI: 10.1007/978-1-4615-5177-5_13.Peer-Reviewed Original ResearchSite-specific genome modificationGenome modificationSpecific DNA sequencesExpression of genesLevel of DNAMammalian cellsHomologous recombinationDNA sequencesGene replacementGene expressionLiving cellsTriplex technologyTriplex formingSpecific sitesDNARecombinationExpressionInitial stepCellsMutagenesisGenesMutationsModificationSitesSequence
1993
Targeted mutagenesis of simian virus 40 DNA mediated by a triple helix-forming oligonucleotide
Havre P, Glazer P. Targeted mutagenesis of simian virus 40 DNA mediated by a triple helix-forming oligonucleotide. Journal Of Virology 1993, 67: 7324-7331. PMID: 8230456, PMCID: PMC238196, DOI: 10.1128/jvi.67.12.7324-7331.1993.Peer-Reviewed Original ResearchConceptsTriple helix-forming oligonucleotidesTarget genesTranscription factor accessViral genomeTransient expression assaysSimian virus 40 DNASequence-specific mannerDNA sequence analysisGene functionFactor accessMammalian cellsGenetic manipulationHomopurine/homopyrimidineTargeted base pairsPromoter sitesTriple-helical DNAExpression assaysGenetic engineeringGene expressionTargeted mutationsSequence analysisMutagenesisHeritable effectsSV40 DNAGenome