Featured Publications
Insights into RAG Evolution from the Identification of “Missing Link” Family A RAGL Transposons
Martin E, Le Targa L, Tsakou-Ngouafo L, Fan T, Lin C, Xiao J, Huang Z, Yuan S, Xu A, Su Y, Petrescu A, Pontarotti P, Schatz D. Insights into RAG Evolution from the Identification of “Missing Link” Family A RAGL Transposons. Molecular Biology And Evolution 2023, 40: msad232. PMID: 37850912, PMCID: PMC10629977, DOI: 10.1093/molbev/msad232.Peer-Reviewed Original ResearchConceptsJawed vertebratesTransposon familyRAG1-RAG2 recombinaseRecombination signal sequencesHemichordate Ptychodera flavaMolecular domesticationSignal sequenceP. flavaDNA bindingPtychodera flavaSequence featuresTransposition activityVertebratesTransposonCritical enzymeHinge regionGenomeDomesticationFlavaProteinPivotal stepAdaptive immunityCritical intermediateRAGRAGLStructural 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 ResearchMeSH KeywordsAnimalsDNA Transposable ElementsEvolution, MolecularGenes, RAG-1Homeodomain ProteinsHumansRecombinasesVertebratesConceptsRAG 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
Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination
Huang S, Tao X, Yuan S, Zhang Y, Li P, Beilinson HA, Zhang Y, Yu W, Pontarotti P, Escriva H, Le Petillon Y, Liu X, Chen S, Schatz DG, Xu A. Discovery of an Active RAG Transposon Illuminates the Origins of V(D)J Recombination. Cell 2016, 166: 102-114. PMID: 27293192, PMCID: PMC5017859, DOI: 10.1016/j.cell.2016.05.032.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsDNA Transposable ElementsDNA-Binding ProteinsEvolution, MolecularHomeodomain ProteinsLanceletsTerminal Repeat SequencesV(D)J RecombinationConceptsRAG transposonAntigen receptor gene assemblyBasal extant chordateDNA transposon familiesVertebrate adaptive immunityRecombination signal sequencesExtant chordatesTarget site duplicationsTransposable elementsDNA recombinationSignal sequenceTransposon excisionGene assemblyProtoRAGTransposon familySite duplicationsCrucial eventTransposonRecombinationAdaptive immunityChordatesTIRLanceletsRAG1/2GermlineCollaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination
Carmona LM, Fugmann SD, Schatz DG. Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination. Genes & Development 2016, 30: 909-917. PMID: 27056670, PMCID: PMC4840297, DOI: 10.1101/gad.278432.116.Peer-Reviewed Original ResearchConceptsRecombination-activating gene 1Transib transposaseAbsence of RAG2RAG1/RAG2Antigen receptor genesJawed vertebratesRAG2 proteinsTransposable elementsRAG1 proteinRegulatory featuresDNA substratesGene 1RAG2Receptor geneRecombination activityProteinRecombinationTransposaseAdaptive immunityVertebratesTransposonGenesEvolutionLow levelsOrigin
2004
Synapsis of Recombination Signal Sequences Located in cis and DNA Underwinding in V(D)J Recombination
Ciubotaru M, Schatz DG. Synapsis of Recombination Signal Sequences Located in cis and DNA Underwinding in V(D)J Recombination. Molecular And Cellular Biology 2004, 24: 8727-8744. PMID: 15367690, PMCID: PMC516766, DOI: 10.1128/mcb.24.19.8727-8744.2004.Peer-Reviewed Original ResearchMeSH KeywordsDNADNA Transposable ElementsGene RearrangementGenes, ImmunoglobulinHMGB2 ProteinHomeodomain ProteinsKineticsRecombination, GeneticSequence Analysis, DNATime FactorsConceptsRecombination signal sequencesDNA substratesSignal sequenceDNA distortionHigh mobility group proteinsProtein conformational changesSame DNA moleculeDouble-strand DNA cleavageRAG proteinsRAG2 proteinsDNA underwindingGroup proteinsSite of cleavagePreferred substrateConformational changesDNA moleculesDNA cleavageProteinRelaxed substrateUnderwindingRecombinationCleavageSequenceSuch substratesHMG1
2000
The RAG Proteins and V(D)J Recombination: Complexes, Ends, and Transposition
Fugmann S, Lee A, Shockett P, Villey I, Schatz D. The RAG Proteins and V(D)J Recombination: Complexes, Ends, and Transposition. Annual Review Of Immunology 2000, 18: 495-527. PMID: 10837067, DOI: 10.1146/annurev.immunol.18.1.495.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
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 StatementsMeSH KeywordsAnimalsDNA Transposable ElementsDNA-Binding ProteinsEvolution, MolecularHomeodomain ProteinsHumansImmune SystemNuclear ProteinsRecombination, GeneticConceptsTransposable elementsAncestral receptor geneAdaptive immune systemReceptor gene segmentsReceptor geneAntigen receptor genesRAG proteinsRAG2 proteinsChromosomal DNAFunctional transposaseMillion yearsGene segmentsRAG1Dramatic supportImmune systemGenesRecent findingsUnusual structureProteinVertebratesTransposaseRAG2DNAEvolutionRecombination
1998
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
Agrawal A, Eastman Q, Schatz D. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 1998, 394: 744-751. PMID: 9723614, DOI: 10.1038/29457.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodiesBinding SitesB-LymphocytesCatalysisCell LineDNADNA Transposable ElementsDNA, CircularDNA-Binding ProteinsDrug Resistance, MicrobialEvolution, MolecularGene Rearrangement, B-LymphocyteGene Rearrangement, T-LymphocyteHigh Mobility Group ProteinsHomeodomain ProteinsImmune SystemMiceMolecular Sequence DataReceptors, Antigen, T-CellRecombination, GeneticRestriction MappingTransposasesVertebratesConceptsT-cell receptor genesRecombination signalsSequence-specific DNA recognitionAncestral receptor geneComponent gene segmentsSite-specific recombination reactionPiece of DNAEvolutionary divergenceJawless vertebratesRecombination-activating geneTransposable elementsDNA recognitionRetroviral integrationGermline insertionDNA moleculesGenesShort duplicationsDNA cleavageRAG1Gene segmentsTransposition reactionRAG2Receptor geneTarget DNA moleculesTarget DNA