2017
2-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
2013
Oxidative Stress in Mammalian Cells Impinges on the Cysteines Redox State of Human XRCC3 Protein and on Its Cellular Localization
Girard P, Graindorge D, Smirnova V, Rigolet P, Francesconi S, Scanlon S, Sage E. Oxidative Stress in Mammalian Cells Impinges on the Cysteines Redox State of Human XRCC3 Protein and on Its Cellular Localization. PLOS ONE 2013, 8: e75751. PMID: 24116071, PMCID: PMC3793007, DOI: 10.1371/journal.pone.0075751.Peer-Reviewed Original ResearchConceptsHomologous recombinationSensitivity to camptothecinCysteine to serineInhibition of DNA replicationCysteine redox stateExposure to camptothecinCellular reducing systemsTargets of ROSIn silico predictionMutant proteinsRAD51 paralogsGenome stabilitySubcellular localizationNon-reducing SDS-PAGEDNA replicationIncreased electrophoretic mobilityMutated proteinChromatin fractionHR pathwayCamptothecin treatmentCysteine residuesInduce DNA damageHuman cellsCellular localizationCHO cells