Featured Publications
Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase
Zhang Y, Corbett E, Wu S, Schatz DG. Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase. The EMBO Journal 2020, 39: e105857. PMID: 32945578, PMCID: PMC7604617, DOI: 10.15252/embj.2020105857.Peer-Reviewed Original ResearchConceptsTarget site DNASite DNARAG1/RAG2 recombinaseSuppression of transpositionCryo-electron microscopyStrand transfer complexAntigen receptor genesDomesticated transposaseTarget DNARAG recombinaseEvolutionary adaptationPaste transpositionStructural basisTransposition activityMechanistic principlesFunctional assaysTransposon endDNAReceptor geneBase unstackingDomesticationTransposaseRecombinaseAdaptive immunityFinal stepStructures of a RAG-like transposase during cut-and-paste transposition
Liu C, Yang Y, Schatz DG. Structures of a RAG-like transposase during cut-and-paste transposition. Nature 2019, 575: 540-544. PMID: 31723264, PMCID: PMC6872938, DOI: 10.1038/s41586-019-1753-7.Peer-Reviewed Original ResearchConceptsCryo-electron microscopy structureC-terminal tailUnique structural elementsStrand transfer complexEukaryotic cutEvolutionary progenitorsMicroscopy structureRAG recombinasePaste transpositionApo enzymeSubstrate DNAHelicoverpa zeaConformational changesEarly stepsTransposaseAdaptive immune systemDNATarget siteTransposonTarget DNAPivotal roleActive siteEnzymeTransposition processEssential component
2018
DNA melting initiates the RAG catalytic pathway
Ru H, Mi W, Zhang P, Alt FW, Schatz DG, Liao M, Wu H. DNA melting initiates the RAG catalytic pathway. Nature Structural & Molecular Biology 2018, 25: 732-742. PMID: 30061602, PMCID: PMC6080600, DOI: 10.1038/s41594-018-0098-5.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesDNA meltingCryo-EM structureBase-specific contactsSignal sequenceDNA transpositionSubstrate bindingRetroviral integrationRAG endonucleaseDimer openingTerminal sequenceGTG sequenceDNA cleavageScissile phosphateDNAUniversal mechanismPiston-like movementSequenceActive siteHeptamerRetrotransposonsCatalytic pathwayTransposonComplexesEndonuclease
2013
Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA
Little AJ, Corbett E, Ortega F, Schatz DG. Cooperative recruitment of HMGB1 during V(D)J recombination through interactions with RAG1 and DNA. Nucleic Acids Research 2013, 41: 3289-3301. PMID: 23325855, PMCID: PMC3597659, DOI: 10.1093/nar/gks1461.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesFluorescence anisotropy experimentsRAG-RSS complexesHigh mobility group box proteinAbsence of DNAGroup box proteinArchitectural proteinsPulldown experimentsRAG2 bindBox proteinSignal sequenceCooperative recruitmentComplex assemblyRecombinase complexStable integrationSequence specificitySynergistic binding effectAnisotropy experimentsAddition of DNAOrder of eventsRAG1DNAHMGB1 proteinProteinConcentration-dependent manner
2009
Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis
Yin FF, Bailey S, Innis CA, Ciubotaru M, Kamtekar S, Steitz TA, Schatz DG. Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis. Nature Structural & Molecular Biology 2009, 16: 499-508. PMID: 19396172, PMCID: PMC2715281, DOI: 10.1038/nsmb.1593.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsBase SequenceChromosome PairingCrystallography, X-RayDNAFluorescence Resonance Energy TransferHomeodomain ProteinsMiceModels, MolecularMolecular Sequence DataNucleic Acid ConformationProtein MultimerizationProtein Structure, QuaternaryProtein Structure, TertiarySolutionsStatic Electricity
2007
Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates*
Yang SY, Fugmann SD, Gramlich HS, Schatz DG. Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates*. Journal Of Biological Chemistry 2007, 282: 25308-25313. PMID: 17613522, DOI: 10.1074/jbc.m704231200.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseChicken B cell line DT40B cell line DT40Cytidine deaminaseNon-Ig lociNon-Ig genesSequence diversificationDNA substratesTranscription cassetteMutation targetsCassetteMolecular characteristicsMolecular featuresDeaminaseDT40TranscriptionGenesLociDNADiversificationMutabilityTargetingIgTarget
2005
Biochemistry of V(D)J Recombination
Schatz DG, Spanopoulou E. Biochemistry of V(D)J Recombination. Current Topics In Microbiology And Immunology 2005, 290: 49-85. PMID: 16480039, DOI: 10.1007/3-540-26363-2_4.Peer-Reviewed Original Research
2003
Regulation of RAG1/RAG2‐mediated transposition by GTP and the C‐terminal region of RAG2
Tsai C, Schatz DG. Regulation of RAG1/RAG2‐mediated transposition by GTP and the C‐terminal region of RAG2. The EMBO Journal 2003, 22: 1922-1930. PMID: 12682024, PMCID: PMC154477, DOI: 10.1093/emboj/cdg185.Peer-Reviewed Original ResearchConceptsFull-length RAG2RAG2 proteinsRegulatory mechanismsC-terminal regionRAG proteinsHybrid joint formationDNA recognitionDNA transpositionCleavage functionChromosomal translocationsGTPUnknown mechanismRAG2ProteinTarget DNAPhysiological concentrationsRegulationJoint formationRAGRAG1MechanismTranslocationDNAGuanineTransposition
1999
Transposition mediated by RAG1 and RAG2 and the evolution of the adaptive immune system
Schatz D. Transposition mediated by RAG1 and RAG2 and the evolution of the adaptive immune system. Immunologic Research 1999, 19: 169-182. PMID: 10493171, DOI: 10.1007/bf02786485.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTransposable elementsAncestral receptor geneAdaptive immune systemReceptor gene segmentsReceptor geneAntigen receptor genesRAG proteinsRAG2 proteinsChromosomal DNAFunctional transposaseMillion yearsGene segmentsRAG1Dramatic supportImmune systemGenesRecent findingsUnusual structureProteinVertebratesTransposaseRAG2DNAEvolutionRecombination
1997
Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage
Eastman Q, Schatz D. Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage. Nucleic Acids Research 1997, 25: 4370-4378. PMID: 9336470, PMCID: PMC147051, DOI: 10.1093/nar/25.21.4370.Peer-Reviewed Original Research
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
1989
The V(D)J recombination activating gene, RAG-1
Schatz D, Oettinger M, Baltimore D. The V(D)J recombination activating gene, RAG-1. Cell 1989, 59: 1035-1048. PMID: 2598259, DOI: 10.1016/0092-8674(89)90760-5.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCell LineCloning, MolecularDNA NucleotidyltransferasesGene Expression RegulationGene LibraryGene Rearrangement, T-LymphocyteGenes, ImmunoglobulinGenomic LibraryHumansMiceMolecular Sequence DataNucleic Acid HybridizationOligonucleotide ProbesReceptors, Antigen, T-CellRecombination, GeneticSequence Homology, Nucleic AcidT-LymphocytesTransfectionVDJ Recombinases