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 intermediateRAGRAGL
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
2016
RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2
Maman Y, Teng G, Seth R, Kleinstein SH, Schatz DG. RAG1 targeting in the genome is dominated by chromatin interactions mediated by the non-core regions of RAG1 and RAG2. Nucleic Acids Research 2016, 44: 9624-9637. PMID: 27436288, PMCID: PMC5175335, DOI: 10.1093/nar/gkw633.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesChromatinChromatin ImmunoprecipitationGenomeGenomic InstabilityHigh-Throughput Nucleotide SequencingHistonesHomeodomain ProteinsHumansMiceNucleotide MotifsPromoter Regions, GeneticProtein BindingProtein Interaction Domains and MotifsRecombination, GeneticV(D)J RecombinationConceptsAntigen receptor lociNon-core regionsReceptor locusPlant homeodomain (PHD) fingerChIP-seq dataWide bindingChromatin interactionsAdditional chromatinLysine 4Off-target activityGenomic featuresHistone 3Novel roleRAG1LociChromatinGenomeRAG2Observed patternsDistinct modesBindingH3K4me3H3K27acEndonucleaseRelative contribution
2015
Histone reader BRWD1 targets and restricts recombination to the Igk locus
Mandal M, Hamel KM, Maienschein-Cline M, Tanaka A, Teng G, Tuteja JH, Bunker JJ, Bahroos N, Eppig JJ, Schatz DG, Clark MR. Histone reader BRWD1 targets and restricts recombination to the Igk locus. Nature Immunology 2015, 16: 1094-1103. PMID: 26301565, PMCID: PMC4575638, DOI: 10.1038/ni.3249.Peer-Reviewed Original ResearchRAG Represents a Widespread Threat to the Lymphocyte Genome
Teng G, Maman Y, Resch W, Kim M, Yamane A, Qian J, Kieffer-Kwon KR, Mandal M, Ji Y, Meffre E, Clark MR, Cowell LG, Casellas R, Schatz DG. RAG Represents a Widespread Threat to the Lymphocyte Genome. Cell 2015, 162: 751-765. PMID: 26234156, PMCID: PMC4537821, DOI: 10.1016/j.cell.2015.07.009.Peer-Reviewed Original ResearchConceptsRecombination signalsStrong recombination signalGenome stabilityHuman genomeActive promotersGenomeDNA damageChromosomal translocationsCleavage siteWidespread threatRAG1Lymphocyte genomeEvolutionary struggleRecombinationRAGChromatinPromoterEndonucleaseSitesRAG2TranslocationAbundanceDepletionEnhancerHeptamer
2008
Two levels of protection for the B cell genome during somatic hypermutation
Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, Kleinstein SH, Schatz DG. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451: 841-845. PMID: 18273020, DOI: 10.1038/nature06547.Peer-Reviewed Original ResearchConceptsError-free DNA repairB cell genomeGenomic stabilityNumerous oncogenesDNA repairCell genomeBase excisionGenomeMismatch repairImmunoglobulin genesSomatic hypermutationWidespread mutationsHypermutationB-cell tumorsB-cell malignanciesHigh-affinity antibodiesB cellsGenesOncogeneLarge fractionDiversityVital roleMutationsEnzymeRepair
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 reactionRecombinationNew concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2
Chatterji M, Tsai C, Schatz DG. New concepts in the regulation of an ancient reaction: transposition by RAG1/RAG2. Immunological Reviews 2004, 200: 261-271. PMID: 15242411, DOI: 10.1111/j.0105-2896.2004.00167.x.Peer-Reviewed Original ResearchConceptsRAG proteinsRecombination-activating gene 1Transposition activityAntigen receptor lociDNA double-stand breaksRAG1/RAG2Lymphoid-specific factorsDouble-stand breaksEndonuclease activityGene 1Chromosomal translocationsVariety of mechanismsProteinSpecific sitesRAG2Ancient reactionRecombinationRecent studiesGenome