Featured Publications
The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination
Beilinson HA, Glynn RA, Yadavalli AD, Xiao J, Corbett E, Saribasak H, Arya R, Miot C, Bhattacharyya A, Jones JM, Pongubala JMR, Bassing CH, Schatz DG. The RAG1 N-terminal region regulates the efficiency and pathways of synapsis for V(D)J recombination. Journal Of Experimental Medicine 2021, 218: e20210250. PMID: 34402853, PMCID: PMC8374863, DOI: 10.1084/jem.20210250.Peer-Reviewed Original Research
2024
RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire
Naik A, Dauphars D, Corbett E, Simpson L, Schatz D, Krangel M. RORγt up-regulates RAG gene expression in DP thymocytes to expand the Tcra repertoire. Science Immunology 2024, 9: eadh5318. PMID: 38489350, PMCID: PMC11005092, DOI: 10.1126/sciimmunol.adh5318.Peer-Reviewed Original ResearchConceptsRecombination activating geneDP thymocytesUp-regulatedAntigen receptor lociDouble-positive (DP) stageRAG expressionTranscriptional up-regulationDouble-negative (DNRAG gene expressionActive genesTcra repertoireReceptor locusDN thymocytesGene expressionThymocyte transitionLymphocyte developmentThymocyte proliferationPhysiological importanceMultiple pathwaysRORgtThymocytesExpressionRepertoireRecombinationAntisilencingChapter 2 The Mechanism, Regulation and Evolution of V(D)J Recombination
Schatz D, Zhang Y, Xiao J, Zha S, Zhang Y, Alt F. Chapter 2 The Mechanism, Regulation and Evolution of V(D)J Recombination. 2024, 13-57. DOI: 10.1016/b978-0-323-95895-0.00004-0.Peer-Reviewed Original ResearchAntigen receptor lociNon-homologous end joiningChromatin loop extrusionRecombination-activating geneLoop extrusionV(D)J recombinationRecombination-activating gene proteinV(D)J recombination reactionReceptor locusEnd joiningDouble-strand (ds) DNA breaksLoop extrusion mechanismRegulation of recombinationRepertoire of antigen receptorsLymphocyte developmentOncogenic chromosomal translocationsVariable region gene segmentsDNA repair proteinsDNA repair pathwaysChromatin accessibilityDNA segmentsV(D)J recombinase activitySubstrate DNALoop domainV(D)J junctions
2016
The Role of RAG in V(D)J Recombination
Carmona L, Schatz D. The Role of RAG in V(D)J Recombination. 2016, 99-106. DOI: 10.1016/b978-0-12-374279-7.05012-8.Peer-Reviewed Original ResearchRecombination signal sequencesTransposable elementsCell cycle-dependent mannerAntigen receptor gene segmentsLymphoid-specific proteinsDNA cleavageCycle-dependent mannerReceptor gene segmentsRAG cleavageRAG proteinsTranslational regulationPosttranslational modificationsSignal sequenceNonhomologous endRAG activitySequence elementsEnhancer elementsTransposition mechanismCell cycleLymphocyte developmentGene segmentsPair of hairpinsBlunt endsRecombinationRAG2
2015
Chapter One Regulation and Evolution of the RAG Recombinase
Teng G, Schatz DG. Chapter One Regulation and Evolution of the RAG Recombinase. Advances In Immunology 2015, 128: 1-39. PMID: 26477364, DOI: 10.1016/bs.ai.2015.07.002.Peer-Reviewed Original ResearchConceptsRAG activityOverall genome integrityDNA breakageSpecific DNA motifsAntigen receptor lociDNA repair pathwaysChapter One RegulationAntigen receptor genesEarly lymphocyte developmentCell cycle statusGenome integrityChromatin structureRAG recombinaseRAG2 proteinsDNA motifsSpatial regulationWidespread bindingRepair pathwaysDNA cleavage activityRecombination eventsShuffling reactionEnzymatic potentialRAG endonucleaseReceptor locusLymphocyte developmentSingle-molecule analysis of RAG-mediated V(D)J DNA cleavage
Lovely GA, Brewster RC, Schatz DG, Baltimore D, Phillips R. Single-molecule analysis of RAG-mediated V(D)J DNA cleavage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e1715-e1723. PMID: 25831509, PMCID: PMC4394307, DOI: 10.1073/pnas.1503477112.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSingle-molecule assaysSame DNA moleculeAntigen receptor genesConsensus recombination signal sequencesSingle-molecule analysisHigh mobility group box protein 1Individual molecular eventsSignal sequenceSingle-molecule levelGene productsDNA bindingMolecular eventsLymphocyte developmentDNA moleculesDNA cleavageProtein 1Synapse formationSynaptic complexReceptor geneCleavageRAGAssaysRAG1/2ComplexesChapter 2 The Mechanism of V(D)J Recombination
Little A, Matthews A, Oettinger M, Roth D, Schatz D. Chapter 2 The Mechanism of V(D)J Recombination. 2015, 13-34. DOI: 10.1016/b978-0-12-397933-9.00002-3.ChaptersLymphocyte developmentNonhomologous end-joining pathwayRegulation of recombinationAntigen receptor lociEnd-joining pathwayDNA repair proteinsRecombination-activating gene 1RAG proteinsDNA breaksRecombinase machineryFunctional antigen receptorEnd processingReceptor locusGenetic instabilityGene 1Recombinase activityChromosomal translocationsDNA cleavageProtein 1Diverse repertoireRepair stepsBox protein 1Antigen receptorHigh mobility group box protein 1Recombination
2011
V(D)J Recombination: Mechanisms of Initiation
Schatz DG, Swanson PC. V(D)J Recombination: Mechanisms of Initiation. Annual Review Of Genetics 2011, 45: 167-202. PMID: 21854230, DOI: 10.1146/annurev-genet-110410-132552.Peer-Reviewed Original ResearchConceptsProtein-DNA complexesUbiquitin ligase activityHistone recognitionDomain organizationRAG proteinsRAG2 proteinsLigase activityT-cell receptor genesRecombination signalsDNA breaksHeptamer sequenceLymphocyte developmentDNA breakageDNA cleavageGene segmentsFunctional significanceProper repairReceptor geneRAG1ProteinRecombinationMechanism of initiationComplexesRecent advancesGenes
2009
Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation
Giblin W, Chatterji M, Westfield G, Masud T, Theisen B, Cheng HL, DeVido J, Alt FW, Ferguson DO, Schatz DG, Sekiguchi J. Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutation. Blood 2009, 113: 2965-2975. PMID: 19126872, PMCID: PMC2662642, DOI: 10.1182/blood-2008-07-165167.Peer-Reviewed Original ResearchConceptsDouble-strand breaksHypomorphic RAG1 mutationsImmune system dysfunctionDNA rearrangementsKnockin mouse modelP53 mutant backgroundAberrant DNA rearrangementsDNA double-strand breaksPremature immunosenescenceDNA end processingSystem dysfunctionRecombination signal sequencesMouse modelRAG1 mutationsImmune systemMice exhibitAntigen receptor genesThymic lymphomasTumor developmentVivo evidenceMutant backgroundLymphocyte developmentSignal sequenceReceptor geneHypomorphic mutations
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
2004
Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes
Shockett PE, Zhou S, Hong X, Schatz DG. Partial reconstitution of V(D)J rearrangement and lymphocyte development in RAG-deficient mice expressing inducible, tetracycline-regulated RAG transgenes. Molecular Immunology 2004, 40: 813-829. PMID: 14687938, DOI: 10.1016/j.molimm.2003.09.009.Peer-Reviewed Original ResearchConceptsPeripheral lymphoid organsIGK locusInducible gene expressionLymph nodesCell reconstitutionLymphoid organsTransgenic miceTRB locusTRD locusT-cell reconstitutionB-cell reconstitutionMammalian cellsRAG-deficient miceSignal endsTra locusRecombination signalsInducible activationGene expressionTCR beta chainFunctional expressionLymphocyte developmentLociRAG2 mRNALymphocyte reconstitutionTransgene
2003
A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences
Lee AI, Fugmann SD, Cowell LG, Ptaszek LM, Kelsoe G, Schatz DG. A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences. PLOS Biology 2003, 1: e1. PMID: 14551903, PMCID: PMC212687, DOI: 10.1371/journal.pbio.0000001.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSignal sequenceGene segmentsProtein-DNA interactionsLevel of recombinationDegree of conservationParticular functional importanceJ gene segmentsAntigen receptor genesSpacer variantsRAG proteinsRecombination machineryRSS activityInactive pseudogeneRSS functionSpacer sequencesFunctional analysisInteraction surfaceFunctional importanceLymphocyte developmentNumerous complex interactionsBiochemical assaysDistinct cooperationReceptor geneHeptamer
1996
rag-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
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
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