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 growth2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity
Sulkowski PL, Corso CD, Robinson ND, Scanlon SE, Purshouse KR, Bai H, Liu Y, Sundaram RK, Hegan DC, Fons NR, Breuer GA, Song Y, Mishra-Gorur K, De Feyter HM, de Graaf RA, Surovtseva YV, Kachman M, Halene S, Günel M, Glazer PM, Bindra RS. 2-Hydroxyglutarate produced by neomorphic IDH mutations suppresses homologous recombination and induces PARP inhibitor sensitivity. Science Translational Medicine 2017, 9 PMID: 28148839, PMCID: PMC5435119, DOI: 10.1126/scitranslmed.aal2463.Peer-Reviewed Original ResearchConceptsIsocitrate dehydrogenase 1PARP inhibitor sensitivityPossible therapeutic strategiesHomologous recombination defectsTherapeutic strategiesTumor xenograftsInhibitor sensitivityPathologic processesSmall molecule inhibitorsIDH1/2 mutationsTumor progressionIDH2 mutationsMutant IDHPolymerase inhibitorsGlioma cellsTumor cellsHR deficiencyPARP inhibitionIDH mutationsInhibitory effectDehydrogenase 1Neomorphic activityMutant IDH1 enzymeDependent dioxygenasesMutant cells
2015
Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment
Scanlon SE, Glazer PM. Multifaceted control of DNA repair pathways by the hypoxic tumor microenvironment. DNA Repair 2015, 32: 180-189. PMID: 25956861, PMCID: PMC4522377, DOI: 10.1016/j.dnarep.2015.04.030.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsDNA repair pathwaysRepair pathwaysDNA repairCertain DNA repair genesMost DNA repair pathwaysDNA double-strand break repairDouble-strand break repairPost-translational modificationsNucleotide excision repairDNA repair genesTumor suppressor geneMultifaceted controlTranslational downregulationEpigenetic levelBreak repairMutator phenotypeCellular consequencesGenomic instabilityExcision repairHypoxic cancer cellsSuppressor geneIntra-tumor heterogeneityMismatch repairPersistent silencingDNA damage