Featured Publications
Structural insights into the evolution of the RAG recombinase
Liu C, Zhang Y, Liu CC, Schatz DG. Structural insights into the evolution of the RAG recombinase. Nature Reviews Immunology 2021, 22: 353-370. PMID: 34675378, DOI: 10.1038/s41577-021-00628-6.Peer-Reviewed Original ResearchConceptsRAG recombinaseComparative genome analysisGenomes of eukaryotesProtein-DNA complexesSingle amino acid mutationAntigen receptor genesMolecular domesticationRag familyAmino acid mutationsJawed vertebratesVertebrate immunityTransposable elementsEvolutionary adaptationGenome analysisStructural biologyDNA bindingStructural insightsGene 1Acid mutationsCleavage activityRecombinaseReceptor geneStructural evidenceRecombinationAdaptive immunityTransposon molecular domestication and the evolution of the RAG recombinase
Zhang Y, Cheng TC, Huang G, Lu Q, Surleac MD, Mandell JD, Pontarotti P, Petrescu AJ, Xu A, Xiong Y, Schatz DG. Transposon molecular domestication and the evolution of the RAG recombinase. Nature 2019, 569: 79-84. PMID: 30971819, PMCID: PMC6494689, DOI: 10.1038/s41586-019-1093-7.Peer-Reviewed Original ResearchConceptsRAG1-RAG2 recombinaseMolecular domesticationRAG recombinaseCryo-electron microscopy structureTwo-tiered mechanismAmino acid residuesJawed vertebratesMicroscopy structureEvolutionary adaptationDNA substratesTransposition activityAcid residuesDomesticationDNA cleavageAcidic regionDiverse repertoireAdaptive immune systemRecombinaseTransposonCell receptorTransposasePivotal eventRecombinationCleavageVertebrates
2017
New insights into the evolutionary origins of the recombination‐activating gene proteins and V(D)J recombination
Carmona LM, Schatz DG. New insights into the evolutionary origins of the recombination‐activating gene proteins and V(D)J recombination. The FEBS Journal 2017, 284: 1590-1605. PMID: 27973733, PMCID: PMC5459667, DOI: 10.1111/febs.13990.Peer-Reviewed Original ResearchConceptsTransposable elementsEvolutionary originRAG proteinsAbsence of RAG2Independent evolutionary originsBasal chordate amphioxusRecombination-activating gene (RAG) proteinsFamily of transposasesAntigen receptor genesRAG transposonChordate amphioxusJawed vertebratesSequence similarityEvolutionary relativesProteins RAG1RAG genesGene proteinRAG1Gene segmentsDiverse arrayMechanistic linkProteinRAG2Adaptive immune systemDNA cleavage reaction
2016
Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies
Brauer PM, Pessach IM, Clarke E, Rowe JH, Ott de Bruin L, Lee YN, Dominguez-Brauer C, Comeau AM, Awong G, Felgentreff K, Zhang YH, Bredemeyer A, Al-Herz W, Du L, Ververs F, Kennedy M, Giliani S, Keller G, Sleckman BP, Schatz DG, Bushman FD, Notarangelo LD, Zúñiga-Pflücker JC. Modeling altered T-cell development with induced pluripotent stem cells from patients with RAG1-dependent immune deficiencies. Blood 2016, 128: 783-793. PMID: 27301863, PMCID: PMC4982452, DOI: 10.1182/blood-2015-10-676304.Peer-Reviewed Original ResearchConceptsInduced pluripotent stem cellsT cell developmentPluripotent stem cellsT cell receptorStem cellsOmenn syndrome patientsSingle-strand DNA breaksHuman induced pluripotent stem cellsControl iPSCsDeep-sequencing analysisT lineage cellsHuman T-cell developmentT cell progenitorsIPSC-derived cellsJoining genesImpaired T-cell differentiationDNA breaksSame geneN-terminalImmune system developmentLocus rearrangementT cell differentiationPatient cellsRecombination activityGenetic defects
2011
A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation
Seitan VC, Hao B, Tachibana-Konwalski K, Lavagnolli T, Mira-Bontenbal H, Brown KE, Teng G, Carroll T, Terry A, Horan K, Marks H, Adams DJ, Schatz DG, Aragon L, Fisher AG, Krangel MS, Nasmyth K, Merkenschlager M. A role for cohesin in T-cell-receptor rearrangement and thymocyte differentiation. Nature 2011, 476: 467-471. PMID: 21832993, PMCID: PMC3179485, DOI: 10.1038/nature10312.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DifferentiationChromosomal Proteins, Non-HistoneDNA-Binding ProteinsGene Expression RegulationGene Rearrangement, T-LymphocyteGenes, RAG-1MiceNuclear ProteinsPhosphoproteinsReceptors, Antigen, T-Cell, alpha-betaRecombinasesThymus GlandTranscription, GeneticRecombination centres and the orchestration of V(D)J recombination
Schatz DG, Ji Y. Recombination centres and the orchestration of V(D)J recombination. Nature Reviews Immunology 2011, 11: 251-263. PMID: 21394103, DOI: 10.1038/nri2941.Peer-Reviewed Original ResearchConceptsAntigen receptor genesRecombination signal sequencesSignal sequenceHigher-order chromatin architectureHistone H3 lysine 4Receptor geneAntigen receptor gene segmentsInactive nuclear compartmentsPlant homeodomain (PHD) fingerH3 lysine 4Antigen receptor lociReceptor gene segmentsEctopic recruitmentChromatin architectureChromatin structureLysine 4Active chromatinGenome instabilityHistone modificationsRAG2 proteinsThousands of sitesNuclear compartmentRecombination eventsTranscriptional activityGenomic DNA
2004
V(D)J recombination
Schatz DG. V(D)J recombination. Immunological Reviews 2004, 200: 5-11. PMID: 15242391, DOI: 10.1111/j.0105-2896.2004.00173.x.Peer-Reviewed Original Research
2003
Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments
Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG. Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments. Genes & Development 2003, 17: 37-42. PMID: 12514097, PMCID: PMC195966, DOI: 10.1101/gad.1031403.Peer-Reviewed Original ResearchAcetylationAllelesAnimalsB-LymphocytesChromatinDNA NucleotidyltransferasesDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Heavy ChainGenes, ImmunoglobulinGenes, RAG-1HistonesHomeodomain ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred C57BLMice, KnockoutPAX5 Transcription FactorTranscription FactorsTranscription, GeneticVDJ Recombinases
2002
RAG1-DNA Binding in V(D)J Recombination SPECIFICITY AND DNA-INDUCED CONFORMATIONAL CHANGES REVEALED BY FLUORESCENCE AND CD SPECTROSCOPY*
Ciubotaru M, Ptaszek LM, Baker GA, Baker SN, Bright FV, Schatz DG. RAG1-DNA Binding in V(D)J Recombination SPECIFICITY AND DNA-INDUCED CONFORMATIONAL CHANGES REVEALED BY FLUORESCENCE AND CD SPECTROSCOPY*. Journal Of Biological Chemistry 2002, 278: 5584-5596. PMID: 12488446, DOI: 10.1074/jbc.m209758200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesCircular DichroismCloning, MolecularDNADNA NucleotidyltransferasesDNA-Binding ProteinsEscherichia coliGenes, RAG-1Homeodomain ProteinsKineticsMiceOligodeoxyribonucleotidesProtein ConformationRecombinant ProteinsRecombination, GeneticSubstrate SpecificityTransfectionTransposasesVDJ RecombinasesConceptsRecombination signal sequencesConformational changesSynaptic complex formationAbsence of DNAAssembly of immunoglobulinMajor conformational changesIntrinsic protein fluorophoresProtein intrinsic fluorescenceSolvent-exposed environmentRAG2 proteinsRAG1/2 complexSingle DNA moleculesRAG1 proteinSignal sequenceAcrylamide quenching studiesT-cell receptor genesStrep-tagRecombination specificityDNA moleculesProtein fluorophoresRAG1Receptor geneProteinIntrinsic fluorescenceCircular dichroismEvidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination
Tsai CL, Drejer AH, Schatz DG. Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombination. Genes & Development 2002, 16: 1934-1949. PMID: 12154124, PMCID: PMC186421, DOI: 10.1101/gad.984502.Peer-Reviewed Original ResearchAlanineAmino Acid SubstitutionAnimalsCell LineCysteineDNADNA NucleotidyltransferasesDNA-Binding ProteinsGene Rearrangement, B-LymphocyteGenes, RAG-1Glutamic AcidHomeodomain ProteinsHumansMacromolecular SubstancesMiceMutagenesis, Site-DirectedNuclear ProteinsNucleic Acid ConformationPhenotypeProtein Interaction MappingRecombinant Fusion ProteinsRecombination, GeneticRegulatory Sequences, Nucleic AcidSerineSubstrate SpecificityVDJ Recombinases
1999
Developing B-cell theories
Schatz D. Developing B-cell theories. Nature 1999, 400: 615-617. PMID: 10458155, DOI: 10.1038/23134.Commentaries, Editorials and Letters
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 animalsExpression
1994
Identifying differences in mRNA expression by representational difference analysis of cDNA
Hubank M, Schatz DG. Identifying differences in mRNA expression by representational difference analysis of cDNA. Nucleic Acids Research 1994, 22: 5640-5648. PMID: 7838717, PMCID: PMC310128, DOI: 10.1093/nar/22.25.5640.Peer-Reviewed Original Research
1992
V(D)J Recombination: Molecular Biology and Regulation
Schatz D, Oettinger M, Schlissel M. V(D)J Recombination: Molecular Biology and Regulation. Annual Review Of Immunology 1992, 10: 359-383. PMID: 1590991, DOI: 10.1146/annurev.iy.10.040192.002043.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements