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 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
2024
The Role of RAG in V(D)J Recombination
Xiao J, Martin E, Wang K, Schatz D. The Role of RAG in V(D)J Recombination. 2024 DOI: 10.1016/b978-0-128-24465-4.00019-3.Peer-Reviewed Original ResearchRecombination signal sequencesRecombination activating geneV(D)J recombinationDNA cleavageConserved sequence elementsNonhomologous end-joining pathwayLymphoid-specific proteinsAntigen receptor gene segmentsEnd-joining pathwayPair of hairpinsReceptor gene segmentsTransposable elementsDomain architectureSequence elementsLocus structureSignal sequenceTransposition mechanismTranscriptional regulationJawed vertebratesTransposase activityActive genesPosttranslational modificationsEnhancer elementsProtein structureCell cycle
2020
Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination
Hirokawa S, Chure G, Belliveau NM, Lovely GA, Anaya M, Schatz DG, Baltimore D, Phillips R. Sequence-dependent dynamics of synthetic and endogenous RSSs in V(D)J recombination. Nucleic Acids Research 2020, 48: gkaa418-. PMID: 32449932, PMCID: PMC7337519, DOI: 10.1093/nar/gkaa418.Peer-Reviewed Original ResearchIdentification 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
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
Collaboration 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
2014
The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells
Karo JM, Schatz DG, Sun JC. The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells. Cell 2014, 159: 94-107. PMID: 25259923, PMCID: PMC4371485, DOI: 10.1016/j.cell.2014.08.026.Peer-Reviewed Original ResearchConceptsRecombination-activating geneDNA damage response mediatorsInnate lymphoid cellsNatural killer cellsAntigen receptor genesCellular fitnessJawed vertebratesRAG recombinaseCellular stressInnate lymphocytesNovel functionDNA breaksKiller cellsEndonuclease activityUnexpected roleCleavage eventsAdaptive immune cellsReceptor geneReduced expressionGenesFunctional heterogeneityCellsImmune cellsResponse mediatorsFitness
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