2019
Cediranib 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
2017
Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells
Scanlon SE, Scanlon CD, Hegan DC, Sulkowski PL, Glazer PM. Nickel induces transcriptional down-regulation of DNA repair pathways in tumorigenic and non-tumorigenic lung cells. Carcinogenesis 2017, 38: 627-637. PMID: 28472268, PMCID: PMC5862357, DOI: 10.1093/carcin/bgx038.Peer-Reviewed Original ResearchConceptsHomology-dependent DNA double-strand break repairDNA repair pathwaysRepair pathwaysHigh-fidelity DNA repair pathwayDNA double-strand break repairMismatch repairDouble-strand break repairDNA double-strand breaksGlobal transcriptional patternsDNA repair proteinsRadiation-induced DNA double-strand breaksDouble-strand breaksTranscriptional repressionDirect DNA damageHost-cell reactivation assayEpigenetic remodelingTranscriptional patternsTranscriptional changesBreak repairDNA mutagenesisGenomic instabilityRepair proteinsHeavy metals nickelLung cellsTumor growth
2014
Hypoxic Stress Facilitates Acute Activation and Chronic Downregulation of Fanconi Anemia Proteins
Scanlon SE, Glazer PM. Hypoxic Stress Facilitates Acute Activation and Chronic Downregulation of Fanconi Anemia Proteins. Molecular Cancer Research 2014, 12: 1016-1028. PMID: 24688021, PMCID: PMC4101147, DOI: 10.1158/1541-7786.mcr-13-0628.Peer-Reviewed Original ResearchConceptsFanconi anemia proteinsDNA repair pathwaysFA pathwayGenomic instabilityRepair pathwaysUbiquitination of FANCD2Intact FA pathwayATR-dependent mannerFA pathway activationAccumulation of γH2AXGenome integrityReplication stressTranscriptional repressionHypoxic conditionsFANCD2Cell survivalDNA damageHypoxic downregulationProtein downregulationHypoxic stressFANCIPathway activationPathwayKey membersCritical role