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 fibroblasts
2018
PTEN Regulates Non-Homologous End Joining by Epigenetic Induction of NHEJ1/XLF
Sulkowski PL, Scanlon SE, Oeck S, Glazer PM. PTEN Regulates Non-Homologous End Joining by Epigenetic Induction of NHEJ1/XLF. Molecular Cancer Research 2018, 16: molcanres.0581.2017. PMID: 29739874, PMCID: PMC6072556, DOI: 10.1158/1541-7786.mcr-17-0581.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCHO CellsCricetinaeCricetulusDNA End-Joining RepairDNA Repair EnzymesDNA-Binding ProteinsEpigenomicsHumansPTEN PhosphohydrolaseConceptsDNA double-strand breaksKey DNA repair pathwaysCytotoxic DNA lesionsXRCC4-like factorPatient-derived melanomasDNA repair pathwaysDouble-strand breaksNovel regulatory roleTumor suppressor geneSuppression of PTENHistone acetyltransferasesDSB repairGenomic analysisNHEJ defectsNonhomologous endRepair pathwaysGene promoterNovel functionRegulatory acetylationNHEJ deficiencyDNA lesionsRegulatory roleSuppressor geneNHEJ DSB repairNHEJ
2015
Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium
McNeer NA, Anandalingam K, Fields RJ, Caputo C, Kopic S, Gupta A, Quijano E, Polikoff L, Kong Y, Bahal R, Geibel JP, Glazer PM, Saltzman WM, Egan ME. Nanoparticles that deliver triplex-forming peptide nucleic acid molecules correct F508del CFTR in airway epithelium. Nature Communications 2015, 6: 6952. PMID: 25914116, PMCID: PMC4480796, DOI: 10.1038/ncomms7952.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell LineChloridesCystic FibrosisCystic Fibrosis Transmembrane Conductance RegulatorDNA-Binding ProteinsGenetic TherapyHigh-Throughput Nucleotide SequencingHumansLactic AcidMice, Inbred C57BLNanoparticlesPeptide Nucleic AcidsPolyglycolic AcidPolylactic Acid-Polyglycolic Acid CopolymerPolymersRespiratory MucosaConceptsFacile genome engineeringVivo gene deliveryBiodegradable polymer nanoparticlesTransient gene expressionNanoparticle systemsGene deliveryPolymer nanoparticlesGene correctionGenome engineeringNanoparticlesOff-target effectsPeptide nucleic acidLethal genetic disorderNucleic acidsDonor DNATarget effectsIntranasal deliveryDeliveryCystic fibrosisEngineeringOligonucleotideChloride effluxHuman cellsAirway epitheliumLung tissue
2001
Hypermutability 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 survivalTriplex-induced Recombination in Human Cell-free Extracts DEPENDENCE ON XPA AND HsRad51*
Datta H, Chan P, Vasquez K, Gupta R, Glazer P. Triplex-induced Recombination in Human Cell-free Extracts DEPENDENCE ON XPA AND HsRad51*. Journal Of Biological Chemistry 2001, 276: 18018-18023. PMID: 11278954, DOI: 10.1074/jbc.m011646200.Peer-Reviewed Original ResearchATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response
Peretz S, Jensen R, Baserga R, Glazer P. ATM-dependent expression of the insulin-like growth factor-I receptor in a pathway regulating radiation response. Proceedings Of The National Academy Of Sciences Of The United States Of America 2001, 98: 1676-1681. PMID: 11172010, PMCID: PMC29316, DOI: 10.1073/pnas.98.4.1676.Peer-Reviewed Original ResearchConceptsWild-type cellsIGF-IR promoter activityAT cellsAtaxia telangiectasiaPromoter activityLevel of transcriptionHeterologous viral promotersDominant negative fragmentTyrosine kinase activityCell surface receptorsATM cDNAIGF-IR expressionIGF-IRInhibition of apoptosisATM functionAT syndromeKinase activityViral promotersCDNA resultsCell transformationInsulin-like growthATM geneSurface receptorsGrowth abnormalitiesExtreme radiosensitivity
2000
Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts
Andrew S, Xu X, Baross-Francis A, Narayanan L, Milhausen K, Liskay R, Jirik F, Glazer P. Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts. Carcinogenesis 2000, 21: 1291-1296. PMID: 10874005, DOI: 10.1093/carcin/21.7.1291.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphatasesAnimalsBase Pair MismatchCrosses, GeneticDNA RepairDNA Repair EnzymesDNA-Binding ProteinsFemaleFrameshift MutationGenes, ReporterGenotypeGerm-Line MutationMaleMiceMice, Inbred BALB CMice, Inbred C57BLMice, KnockoutMice, TransgenicMismatch Repair Endonuclease PMS2MutagenesisMutS Homolog 2 ProteinPoint MutationProteinsProto-Oncogene ProteinsConceptsPms2-deficient miceMsh2-deficient miceHereditary non-polyposis colorectal cancer patientsCII target geneDNA mismatch repair deficiencyColorectal cancer patientsPMS2 germline mutationsMismatch repair deficiencyReporter transgenic miceMutation frequencyLacI target geneCancer patientsTarget genesMouse modelKnockout miceTumor spectrumTransgenic miceFrameshift mutationGermline mutationsMiceRepair deficiencyPMS2 deficiencySupF target geneMSH2Predominant mutationsTriple-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
Different mutator phenotypes in Mlh1- versus Pms2-deficient mice
Yao X, Buermeyer A, Narayanan L, Tran D, Baker S, Prolla T, Glazer P, Liskay R, Arnheim N. Different mutator phenotypes in Mlh1- versus Pms2-deficient mice. Proceedings Of The National Academy Of Sciences Of The United States Of America 1999, 96: 6850-6855. PMID: 10359802, PMCID: PMC22005, DOI: 10.1073/pnas.96.12.6850.Peer-Reviewed Original ResearchConceptsMismatch repairMutator phenotypeMutation rateDifferent chromosomal locationsSingle-molecule PCRDinucleotide repeat lociMutation frequencyDNA mismatch repairMononucleotide repeat tractsChromosomal locationCellular processesDNA repair capacityHigh mutation frequencyDifferent mutator phenotypesMultiple genetic alterationsKnockout strainRepeat tractMlh1pMLH1 MMR geneRepeat lociGenetic alterationsDifferent tumor spectrumRepair capacityTumor developmentMMR genes
1998
Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways.
Turner B, Zhang J, Gumbs A, Maher M, Kaplan L, Carter D, Glazer P, Hurst H, Haffty B, Williams T. Expression of AP-2 transcription factors in human breast cancer correlates with the regulation of multiple growth factor signalling pathways. Cancer Research 1998, 58: 5466-72. PMID: 9850080.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesBreastBreast NeoplasmsDNA-Binding ProteinsEpitheliumFemaleHumansImmunohistochemistryPrognosisPromoter Regions, GeneticReceptor, ErbB-2Receptor, IGF Type 1Receptors, EstrogenReceptors, Growth FactorReceptors, ProgesteroneSignal TransductionTranscription Factor AP-2Transcription FactorsTumor Cells, CulturedUp-RegulationConceptsAP-2 transcription factorsAP-2-binding sitesTranscription factorsAP-2gammaAP-2alphaAP-2 gene familyAP-2 geneAP-2 family membersInsulin-like growth factor I receptorAP-2 familySignal transduction moleculesAP-2 proteinsAP-2alpha proteinMammalian developmentGene familyHuman breast cancerGrowth factor receptorTransduction moleculesProximal promoterBreast cancerReceptor promoterMultiple growth factorsBreast cancer cell linesCell growthAP-2gamma expression
1997
Role of DNA mismatch repair in the cytotoxicity of ionizing radiation.
Fritzell J, Narayanan L, Baker S, Bronner C, Andrew S, Prolla T, Bradley A, Jirik F, Liskay R, Glazer P. Role of DNA mismatch repair in the cytotoxicity of ionizing radiation. Cancer Research 1997, 57: 5143-7. PMID: 9371516.Peer-Reviewed Original ResearchConceptsMammalian cellsCellular responsesCell linesTranscription-coupled repairMMR systemWild-type cellsDNA-damaging agentsWild-type cell linesMMR-deficient cellsDNA mismatch repairDNA mismatch repair systemMismatch repair systemActive genesFutile repairMMR factorsAlkylation damageMismatch repairReplication errorsDNA damageRepair systemRelated miceCancer cellsClonogenic survivalMMR genesGenesElevated 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
1989
UV-induced DNA-binding proteins in human cells.
Glazer P, Greggio N, Metherall J, Summers W. UV-induced DNA-binding proteins in human cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1989, 86: 1163-1167. PMID: 2919165, PMCID: PMC286646, DOI: 10.1073/pnas.86.4.1163.Peer-Reviewed Original ResearchMeSH KeywordsCycloheximideDactinomycinDNA ProbesDNA-Binding ProteinsHeLa CellsHumansMolecular WeightNuclear ProteinsUltraviolet RaysConceptsDose-dependent manner