2022
Chapter 11 Oncometabolites, epigenetic marks, and DNA repair
Dow J, Glazer P. Chapter 11 Oncometabolites, epigenetic marks, and DNA repair. 2022, 191-202. DOI: 10.1016/b978-0-323-91081-1.00008-x.Peer-Reviewed Original ResearchDNA damage repairJmjC domain-containing histone demethylasesDamage repairDouble-strand break sitesHallmarks of cancerEpigenetic marksHistone demethylasesEpigenetic signalingDNA demethylaseDependent dioxygenasesEpigenetic mechanismsDNA repairMajor translational impactGenomic instabilityMethylation signalsRepair pathwaysBreak siteDNA hypermethylationDNA damageΑ-ketoglutarateGlobal histoneOncometaboliteCancer cellsCompetitive inhibitorProfound sensitivity
2020
Oncometabolites suppress DNA repair by disrupting local chromatin signalling
Sulkowski PL, Oeck S, Dow J, Economos NG, Mirfakhraie L, Liu Y, Noronha K, Bao X, Li J, Shuch BM, King MC, Bindra RS, Glazer PM. Oncometabolites suppress DNA repair by disrupting local chromatin signalling. Nature 2020, 582: 586-591. PMID: 32494005, PMCID: PMC7319896, DOI: 10.1038/s41586-020-2363-0.Peer-Reviewed Original ResearchConceptsDNA repairDNA breaksFumarate hydrataseDownstream repair factorsHistone 3 lysine 9Homology-dependent repairPoly (ADP-ribose) polymeraseRecruitment of TIP60Deregulation of metabolismChromatin signalingSuccinate dehydrogenase genesGenome integrityLysine 9Repair factorsDehydrogenase geneEnd resectionIsocitrate dehydrogenase 1Aberrant hypermethylationMechanistic basisSomatic mutationsDehydrogenase 1GenesHuman malignanciesProper executionMutations
2019
Impact of hypoxia on DNA repair and genome integrity
Kaplan AR, Glazer PM. Impact of hypoxia on DNA repair and genome integrity. Mutagenesis 2019, 35: 61-68. PMID: 31282537, PMCID: PMC7317153, DOI: 10.1093/mutage/gez019.Peer-Reviewed Original ResearchConceptsDNA repairDNA repair pathwaysHomology-directed repairBase excision repairGenome integrityRepair pathwaysGenomic instabilityExcision repairHypoxia mimeticMismatch repairDiverse mechanismsImpact of hypoxiaCancer progressionMutation frequencyTumor biologyTumor microenvironmentDevelopment of metastasesPotential clinical relevanceProfound effectRepairBiologyHypoxiaPathwayHallmarkMicroenvironmentCediranib 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
2018
Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair
Sulkowski PL, Sundaram RK, Oeck S, Corso CD, Liu Y, Noorbakhsh S, Niger M, Boeke M, Ueno D, Kalathil AN, Bao X, Li J, Shuch B, Bindra RS, Glazer PM. Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair. Nature Genetics 2018, 50: 1086-1092. PMID: 30013182, PMCID: PMC6072579, DOI: 10.1038/s41588-018-0170-4.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksPGL/PCCDNA repair deficiency syndromeHomologous recombination DNA repair pathwayDNA repair pathwaysDouble-strand breaksHomologous recombination DNA repairSynthetic lethal targetingGenomic integrityDNA repairFumarate hydrataseMechanistic basisCancer predispositionFunction mutationsGermline lossKrebs cycleSuccinate dehydrogenaseHereditary paragangliomaRespectively1–3Ribose polymerase inhibitorsHereditary leiomyomatosisHereditary cancer syndromesCancer syndromesTumor cellsPolymerase inhibitors
2017
A cell-penetrating antibody inhibits human RAD51 via direct binding
Turchick A, Hegan DC, Jensen RB, Glazer PM. A cell-penetrating antibody inhibits human RAD51 via direct binding. Nucleic Acids Research 2017, 45: 11782-11799. PMID: 29036688, PMCID: PMC5714174, DOI: 10.1093/nar/gkx871.Peer-Reviewed Original ResearchConceptsHomology-directed repairMolecular basisDirect bindingSynthetic lethal killingPre-clinical developmentBRCA2-deficient cancer cellsCell-penetrating antibodiesAnti-cancer agentsLupus autoantibodiesHuman Rad51DNA repairDNA bindingRAD51N-terminusCancer cellsSilico molecular modelingFunction mutationsCancer therapySpecific inhibitorDNANovel inhibitorsAttractive targetComplementarity-determining regionsMolecular modelingCell penetration
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
2001
Genomic 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
1999
Targeted 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 ResearchConceptsMammalian 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 linker
1996
Triplex‐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 helix