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 intermediateRAGRAGLTransposon 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 eventRecombinationCleavageVertebratesStructures 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
2020
Identification of RAG-like transposons in protostomes suggests their ancient bilaterian origin
Martin EC, Vicari C, Tsakou-Ngouafo L, Pontarotti P, Petrescu AJ, Schatz DG. Identification of RAG-like transposons in protostomes suggests their ancient bilaterian origin. Mobile DNA 2020, 11: 17. PMID: 32399063, PMCID: PMC7204232, DOI: 10.1186/s13100-020-00214-y.Peer-Reviewed Original ResearchProtostome genomesAdjacent gene pairsProtostome lineageBilaterian evolutionBilaterian ancestorJawed vertebratesProtostome evolutionBilateria cladeEarly deuterostomesEvolutionary historyBilaterian originGene pairsPhylogenetic analysisMultiple duplicationsRAG2 geneProtostomesEvolutionary precursorTransposase activityEarly bilateriansRibbon wormsIntact elementsGenomeDeuterostomesTransposonJ recombination
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
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 ResearchConceptsRAG 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
Antigen receptor genes and the evolution of a recombinase
Schatz DG. Antigen receptor genes and the evolution of a recombinase. Seminars In Immunology 2004, 16: 245-256. PMID: 15522623, DOI: 10.1016/j.smim.2004.08.004.Peer-Reviewed Original ResearchConceptsAntigen receptor genesReceptor geneDNA repair factorsSite-specific recombination reactionRAG transposonVertebrate genomesJawed vertebratesEvolutionary implicationsRAG2 proteinsTransposable elementsRepair factorsGenesAdaptive immune systemHorizontal transmissionRAG1VertebratesGenomeImmune systemTransposonGermlineRecombinaseRAG2ProteinRecombination reactionRecombination