1997
RAG1 and RAG2 Form a Stable Postcleavage Synaptic Complex with DNA Containing Signal Ends in V(D)J Recombination
Agrawal A, Schatz D. RAG1 and RAG2 Form a Stable Postcleavage Synaptic Complex with DNA Containing Signal Ends in V(D)J Recombination. Cell 1997, 89: 43-53. PMID: 9094713, DOI: 10.1016/s0092-8674(00)80181-6.Peer-Reviewed Original ResearchConceptsSignal endsRecombination signalsDNA-dependent protein kinaseProtein-DNA complexesSynaptic complexHMG-2 proteinStable complexesDNA adjacentProtein kinaseProteins RAG1Immunoprecipitation experimentsMobility shiftNuclease sensitivityHMG-1Cleavage systemRAG1RAG2RecombinationComplexesVivo observationsKinaseProteinImportant stepCleavageDefinition of a large region of RAG1 that is important for coimmunoprecipitation of RAG2.
McMahan CJ, Sadofsky MJ, Schatz DG. Definition of a large region of RAG1 that is important for coimmunoprecipitation of RAG2. The Journal Of Immunology 1997, 158: 2202-10. PMID: 9036966, DOI: 10.4049/jimmunol.158.5.2202.Peer-Reviewed Original Research
1996
Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells
Han S, Zheng B, Schatz D, Spanopoulou E, Kelsoe G. Neoteny in Lymphocytes: Rag1 and Rag2 Expression in Germinal Center B Cells. Science 1996, 274: 2094-2097. PMID: 8953043, DOI: 10.1126/science.274.5295.2094.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesDNA NucleotidyltransferasesDNA-Binding ProteinsFemaleGene ExpressionGene RearrangementGenes, ImmunoglobulinGenes, RAG-1Germinal CenterHomeodomain ProteinsImmunizationImmunoglobulin Class SwitchingLymphocyte ActivationMiceMice, Inbred C57BLPolymerase Chain ReactionProtein BiosynthesisProteinsVDJ RecombinasesConceptsGerminal center B cellsAntigen receptor genesT cell antigen receptor genesRAG2 proteinsB cellsRAG2 geneRAG genesRAG2 expressionFunctional immunoglobulinPeyer's patch germinal centersMessenger RNAGenesRAG1Receptor geneActivated B cellsNormal adult animalsLymphocyte populationsImmature lymphocytesGerminal centersBone marrowMurine splenicAntibody repertoireCellsAdult animalsExpressionRAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination
Difilippantonio M, McMahan C, Eastman Q, Spanopoulou E, Schatz D. RAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination. Cell 1996, 87: 253-262. PMID: 8861909, DOI: 10.1016/s0092-8674(00)81343-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell LineDNA NucleotidyltransferasesDNA-Binding ProteinsGenes, ImmunoglobulinHomeodomain ProteinsHumansMacromolecular SubstancesMolecular Sequence DataNuclear ProteinsProtein BindingProteinsRecombinant ProteinsRecombination, GeneticSalmonellaSequence AlignmentStructure-Activity RelationshipTranscriptional ActivationTransfectionConceptsDNA bindingAbsence of RAG2Signal sequence recognitionRegion of RAG1RAG2 proteinsBacterial invertasesSequence similarityRecombination signalsSpecific binding interactionsRAG1Sequence recognitionDNA cleavageRAG2Binding interactionsProteinBindingRecombinationRecent studiesSignal recognitionInvertaseHeptamerRecruitmentCleavageLocalizationVivoA Zinc-binding Domain Involved in the Dimerization of RAG1
Rodgers K, Bu Z, Fleming K, Schatz D, Engelman D, Coleman J. A Zinc-binding Domain Involved in the Dimerization of RAG1. Journal Of Molecular Biology 1996, 260: 70-84. PMID: 8676393, DOI: 10.1006/jmbi.1996.0382.Peer-Reviewed Original ResearchConceptsRecombination-activating gene 1Zinc-binding motifDimerization domainZinc fingerProtein-protein interactionsLymphoid-specific genesN-terminal thirdZinc finger sequencesAmino acid residuesC3HC4 motifRAG1 sequencesRAG1 proteinTerminal domainHomodimer formationAcid residuesBiophysical techniquesGene 1Energetics of associationMonomeric subunitsMotifProteinFinger sequencesSequenceC3HC4Zinc ionsProductive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo.
Hoffman ES, Passoni L, Crompton T, Leu TM, Schatz DG, Koff A, Owen MJ, Hayday AC. Productive T-cell receptor beta-chain gene rearrangement: coincident regulation of cell cycle and clonality during development in vivo. Genes & Development 1996, 10: 948-962. PMID: 8608942, DOI: 10.1101/gad.10.8.948.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, Differentiation, T-LymphocyteCell CycleCell SeparationClone CellsCyclinsDNA-Binding ProteinsFemaleFlow CytometryFluorescent Antibody Technique, IndirectGene Expression Regulation, DevelopmentalGene Rearrangement, beta-Chain T-Cell Antigen ReceptorHomeodomain ProteinsHyaluronan ReceptorsMiceMice, Inbred C57BLProteinsReceptors, Antigen, T-Cell, alpha-betaReceptors, Interleukin-2Retinoblastoma ProteinRNA, MessengerT-LymphocytesThymus GlandConceptsTCRbeta chain genesBeta selectionT-cell receptor beta-chain locusChain geneTCRbeta chain gene rearrangementAlpha beta T cell developmentProductive gene rearrangementHyperphosphorylation of RbGene rearrangementsTCR gene rearrangementsTransition of thymocytesTCRbeta gene rearrangementT cell developmentRegulation of p27Coincident regulationBeta-chain locusPopulation of cellsTCR lociCell cycleCdc2 activityCDK2 activityTCRbeta selectionCyclin AThymocyte expansionCell phenotypeThe half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression.
Grawunder U, Schatz DG, Leu TM, Rolink A, Melchers F. The half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression. Journal Of Experimental Medicine 1996, 183: 1731-1737. PMID: 8666930, PMCID: PMC2192496, DOI: 10.1084/jem.183.4.1731.Peer-Reviewed Original ResearchInitiation of V(D)J recombination in vitro obeying the 12/23 rule
Eastman Q, Leu T, Schatz D. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 1996, 380: 85-88. PMID: 8598914, DOI: 10.1038/380085a0.Peer-Reviewed Original Researchrag-1 and rag-2: Biochemistry and Protein Interactions
Schatz D, Leu T. rag-1 and rag-2: Biochemistry and Protein Interactions. Current Topics In Microbiology And Immunology 1996, 217: 11-29. PMID: 8787615, DOI: 10.1007/978-3-642-50140-1_2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsRAG-1Protein-protein interactionsRAG-2 proteinT-cell receptor proteinsSite-specific recombination reactionLymphocyte-specific factorsProtein interactionsEnzymatic machineryGene productsRAG-2Lymphocyte developmentReceptor proteinBiochemical propertiesProteinCoordinated activityGenesTerminal deoxynucleotidyl transferaseRecombinationDiversityDeoxynucleotidyl transferaseMost componentsMachineryNucleotidesSpeciesTransferase
1995
Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement
Grawunder U, Leu T, Schatz D, Werner A, Rolink A, Melchers F, Winkler T. Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement. Immunity 1995, 3: 601-608. PMID: 7584150, DOI: 10.1016/1074-7613(95)90131-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBase SequenceCell DifferentiationCell LineDNA-Binding ProteinsDown-RegulationFemaleFlow CytometryGene Rearrangement, B-LymphocyteHomeodomain ProteinsImmunoglobulin Heavy ChainsMiceMice, Inbred C57BLMice, Inbred DBAMice, Inbred StrainsMolecular Sequence DataPolymerase Chain ReactionProtein BiosynthesisProteinsProto-Oncogene Proteins c-kitReceptors, Antigen, B-CellRNA, MessengerConceptsRAG2 gene expressionPreB cellsGene expressionFunctional immunoglobulin genesPreB-II cellsPreB cell receptorB cell developmentCell cycle statusHeavy chain allelesRAG2 proteinsPostranscriptional levelImmature B cellsRAG genesGene productsTranscriptional levelProductive rearrangementsMouse bone marrowCell developmentDifferential surface expressionImmunoglobulin genesRAG1Cell surfaceRAG2 mRNAGenesCycle statusrag-1 and rag-2 Are Components of a High-Molecular-Weight Complex, and Association of rag-2 with This Complex Is rag-1 Dependent
Leu T, Schatz D. rag-1 and rag-2 Are Components of a High-Molecular-Weight Complex, and Association of rag-2 with This Complex Is rag-1 Dependent. Molecular And Cellular Biology 1995, 15: 5657-5670. PMID: 7565717, PMCID: PMC230816, DOI: 10.1128/mcb.15.10.5657.Peer-Reviewed Original ResearchConceptsRAG-2RAG-1RAG-2 proteinRAG proteinsSubcellular localizationBiological functionsIntracellular complexesWeight complexesLymphocyte developmentSized complexesBiochemical propertiesProteinCell linesSame complexHigh salt concentrationsSynergistic functionImmunological reagentsNuclear structureComplexesCoimmunoprecipitationHigh-MolecularMore moleculesHigh levelsRecombinationSalt concentration
1993
Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes.
Petrie HT, Livak F, Schatz DG, Strasser A, Crispe IN, Shortman K. Multiple rearrangements in T cell receptor alpha chain genes maximize the production of useful thymocytes. Journal Of Experimental Medicine 1993, 178: 615-622. PMID: 8393478, PMCID: PMC2191132, DOI: 10.1084/jem.178.2.615.Peer-Reviewed Original ResearchConceptsAlpha/beta heterodimerMultiple rearrangementsTCR alpha/beta heterodimerBeta heterodimerBeta chainT-cell receptor alpha-chain geneChain geneTCR alpha geneTCR alphaSurface expressionReceptor alpha-chain geneTransgenic TCR beta chainTCR alpha locusAlpha chain geneT cell receptor alphaAlpha gene rearrangementsMajority of TCREndogenous TCR alpha chainsHeavy chain genePositive selectionSomatic rearrangementsAllelic exclusionAlpha geneAlpha locusTCR alpha chain
1992
The recombination activating genes, RAG 1 and RAG 2, are on chromosome 11p in humans and chromosome 2p in mice
Oettinger M, Stanger B, Schatz D, Glaser T, Call K, Housman D, Baltimore D. The recombination activating genes, RAG 1 and RAG 2, are on chromosome 11p in humans and chromosome 2p in mice. Immunogenetics 1992, 35: 97-101. PMID: 1735560, DOI: 10.1007/bf00189518.Peer-Reviewed Original ResearchConceptsRAG locusChromosome 11pRAG-2RAG-1Human chromosome 11pGenes RAG-1Hybrid cell linesJoining (V(D)J) recombinationChromosomal localizationChromosomal locationAdjacent genesCell hybridsHuman recombinationSouthern analysisChromosome 11Human diseasesGenesChromosome 2pLociCell linesRetardation syndromeRecombinationDeletionHybridsLocalization
1991
Thymocyte Expression of RAG-1 and RAG-2: Termination by T Cell Receptor Cross-Linking
Turka L, Schatz D, Oettinger M, Chun J, Gorka C, Lee K, McCormack W, Thompson C. Thymocyte Expression of RAG-1 and RAG-2: Termination by T Cell Receptor Cross-Linking. Science 1991, 253: 778-781. PMID: 1831564, DOI: 10.1126/science.1831564.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigens, CDAntigens, Differentiation, T-LymphocyteCD3 ComplexCell DifferentiationCell SurvivalDNA NucleotidyltransferasesDNA-Binding ProteinsGene ExpressionGene Rearrangement, T-LymphocyteHomeodomain ProteinsHumansMiceNuclear ProteinsNucleic Acid HybridizationProteinsReceptor AggregationReceptors, Antigen, T-CellReceptors, Interleukin-2RNA, MessengerT-Lymphocyte SubsetsThymus GlandVDJ RecombinasesConceptsMajor histocompatibility complexCortical thymocytesSelf-major histocompatibility complexT cell receptor expressionHLA class IRAG-2Cell receptor expressionTCR complexRAG expressionT cell developmentT cell surfaceThymic subpopulationsCD4-CD8Intact thymusReceptor expressionThymic maturationRAG-1RAG-2 expressionThymocyte TCRThymocyte maturationHistocompatibility complexClass IReceptor crossThymocyte expressionBlot analysis
1990
RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination
Oettinger M, Schatz D, Gorka C, Baltimore D. RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination. Science 1990, 248: 1517-1523. PMID: 2360047, DOI: 10.1126/science.2360047.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCattleCell LineChickensCricetinaeDNADNA NucleotidyltransferasesDNA-Binding ProteinsDogsFemaleGene Rearrangement, B-LymphocyteGene Rearrangement, T-LymphocyteHomeodomain ProteinsHumansMaleMiceMolecular Sequence DataMultigene FamilyNuclear ProteinsNucleic Acid HybridizationOpossumsProteinsRabbitsRecombination, GeneticRestriction MappingTransfectionTurtlesVDJ RecombinasesConceptsRAG-2RAG-1Adjacent genesRecombinase activityFrequency of recombinationPutative proteinUntranslated sequenceSingle exonGenomic rearrangementsExpression patternsVast repertoireGenesComplementary DNAAmino acidsT cell receptorCell receptorRecombinationSequenceKilobasesExonsCotransfectionRecombinaseSpeciesProteinDNA