2019
Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire
Shinoda K, Maman Y, Canela A, Schatz DG, Livak F, Nussenzweig A. Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire. Cell Reports 2019, 29: 4471-4481.e6. PMID: 31875554, PMCID: PMC8214342, DOI: 10.1016/j.celrep.2019.11.088.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksRecombination signal sequencesVκ gene segmentsGene segmentsDouble-strand breaksVariable gene segmentsRAG proteinsSignal sequenceV-J rearrangementRecombination eventsSpacer regionVκ-JκRecombinationLevels of breakageComplete absenceProteinLarge fractionDeletionJκSequence
2017
Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks
Fisher MR, Rivera-Reyes A, Bloch NB, Schatz DG, Bassing CH. Immature Lymphocytes Inhibit Rag1 and Rag2 Transcription and V(D)J Recombination in Response to DNA Double-Strand Breaks. The Journal Of Immunology 2017, 198: 2943-2956. PMID: 28213501, PMCID: PMC5360515, DOI: 10.4049/jimmunol.1601639.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDNA damage responseRAG1/RAG2Double-strand breaksRAG DNA double-strand breaksMultiple genomic locationsTranscription of genesNF-κB transcription factorsDSB responseGenomic integrityGenomic locationATM kinaseTranscriptional repressionRAG cleavageCellular functionsDamage responseLocus recombinationMammalian cellsRAG1 proteinTranscription factorsModulator proteinRAG expressionAtaxia telangiectasiaTranscriptional inhibitionDevelopmental stages
2015
Spatio-temporal regulation of RAG2 following genotoxic stress
Rodgers W, Byrum JN, Sapkota H, Rahman NS, Cail RC, Zhao S, Schatz DG, Rodgers KK. Spatio-temporal regulation of RAG2 following genotoxic stress. DNA Repair 2015, 27: 19-27. PMID: 25625798, PMCID: PMC4336829, DOI: 10.1016/j.dnarep.2014.12.008.Peer-Reviewed Original ResearchMeSH KeywordsActive Transport, Cell NucleusAtaxia Telangiectasia Mutated ProteinsCell NucleusCells, CulturedCentrosomeDNADNA Breaks, Double-StrandedDNA RepairDNA-Binding ProteinsGene Knockdown TechniquesHumansMicroscopy, FluorescenceMutationNuclear ProteinsPrecursor Cells, B-LymphoidRadiation, IonizingSubcellular FractionsVDJ RecombinasesConceptsDNA double-strand breaksGenotoxic stressorsCellular responsesFormation of DSBsLymphocyte antigen receptor genesDNA DSBsSpatio-temporal regulationInhibition of ATMDNA damaging agentsSubcellular fractionation approachDouble-strand breaksAntigen receptor genesNuclear Rag2Genotoxic stressRAG complexDNA repairIncorrect repairDamaging agentsStrand breaksNovel mechanismRAG2Receptor geneCentrosomesFractionation approachSubstantial enrichment
2014
The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells
Karo JM, Schatz DG, Sun JC. The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells. Cell 2014, 159: 94-107. PMID: 25259923, PMCID: PMC4371485, DOI: 10.1016/j.cell.2014.08.026.Peer-Reviewed Original ResearchConceptsRecombination-activating geneDNA damage response mediatorsInnate lymphoid cellsNatural killer cellsAntigen receptor genesCellular fitnessJawed vertebratesRAG recombinaseCellular stressInnate lymphocytesNovel functionDNA breaksKiller cellsEndonuclease activityUnexpected roleCleavage eventsAdaptive immune cellsReceptor geneReduced expressionGenesFunctional heterogeneityCellsImmune cellsResponse mediatorsFitness
2013
The Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements
Steinel NC, Lee BS, Tubbs AT, Bednarski JJ, Schulte E, Yang-Iott KS, Schatz DG, Sleckman BP, Bassing CH. The Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements. Journal Of Experimental Medicine 2013, 210: 233-239. PMID: 23382544, PMCID: PMC3570110, DOI: 10.1084/jem.20121605.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsBase SequenceB-LymphocytesCell Cycle ProteinsDNA Breaks, Double-StrandedDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Light ChainHistonesHomeodomain ProteinsImmunoglobulin kappa-ChainsIntracellular Signaling Peptides and ProteinsMiceMice, 129 StrainMice, KnockoutModels, BiologicalProtein Serine-Threonine KinasesRNA, MessengerSignal TransductionTumor Suppressor ProteinsConceptsDNA double-strand breaksRAG DNA double-strand breaksAllelic exclusionIgκ rearrangementAtaxia telangiectasiaProtein kinase kinaseAntigen receptor chainsDouble-strand breaksHistone H2AX phosphorylationFeedback inhibitionATM kinaseIgκ recombinationKinase kinaseDNA-PKConcomitant repressionH2AX phosphorylationRAG endonucleaseReceptor chainsMDC1H2AXKinaseAllelesRecombinationRearrangementTelangiectasia
2012
Dendritic cell–mediated activation-induced cytidine deaminase (AID)–dependent induction of genomic instability in human myeloma
Koduru S, Wong E, Strowig T, Sundaram R, Zhang L, Strout MP, Flavell RA, Schatz DG, Dhodapkar KM, Dhodapkar MV. Dendritic cell–mediated activation-induced cytidine deaminase (AID)–dependent induction of genomic instability in human myeloma. Blood 2012, 119: 2302-2309. PMID: 22234692, PMCID: PMC3311257, DOI: 10.1182/blood-2011-08-376236.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBlotting, WesternCell Line, TumorCell SurvivalCells, CulturedCoculture TechniquesCytidine DeaminaseDendritic CellsDNA Breaks, Double-StrandedFemaleGene Expression Regulation, EnzymologicGene Expression Regulation, NeoplasticGenomic InstabilityHumansInterleukin Receptor Common gamma SubunitMiceMice, Inbred NODMice, KnockoutMice, SCIDMultiple MyelomaNF-kappa BRANK LigandReverse Transcriptase Polymerase Chain ReactionTransplantation, HeterologousTumor Cells, CulturedConceptsInduction of AIDMultiple myelomaTumor microenvironmentTumor cellsReceptor activatorActivation-induced cytidine deaminaseDendritic cell infiltrationCapacity of DCPrimary MM cellsNF-κB/receptor activatorGenetics of tumorsGrowth of tumorsGenomic damageMyeloma cell linesRANKL inhibitionPlasmacytoid DCsIndolent behaviorCell infiltrationMM cellsHuman myelomaCytidine deaminaseMyelomaDNA double-strand breaksGenomic instabilityCell lines