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
2016
A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin
Janssen A, Breuer GA, Brinkman EK, van der Meulen AI, Borden SV, van Steensel B, Bindra RS, LaRocque JR, Karpen GH. A single double-strand break system reveals repair dynamics and mechanisms in heterochromatin and euchromatin. Genes & Development 2016, 30: 1645-1657. PMID: 27474442, PMCID: PMC4973294, DOI: 10.1101/gad.283028.116.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksHomologous recombinationGenome stabilityHeterochromatic DSBsEuchromatic DSBsSingle DNA double-strand breakMain DSB repair pathwaysDifferent chromatin domainsLarval imaginal discsDistinct nuclear domainsRepetitive DNA sequencesDSB repair pathwaysDouble-strand breaksChromatin contextChromatin domainsEuchromatic lociPericentromeric heterochromatinChromatin regionsHomologous chromosomesHR templateImaginal discsDSB repairDNA sequencesNuclear domainsRepair pathways