Featured Publications
Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase
Zhang Y, Corbett E, Wu S, Schatz DG. Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase. The EMBO Journal 2020, 39: embj2020105857. PMID: 32945578, PMCID: PMC7604617, DOI: 10.15252/embj.2020105857.Peer-Reviewed Original ResearchConceptsTarget site DNASite DNARAG1/RAG2 recombinaseSuppression of transpositionCryo-electron microscopyStrand transfer complexAntigen receptor genesDomesticated transposaseTarget DNARAG recombinaseEvolutionary adaptationPaste transpositionStructural basisTransposition activityMechanistic principlesFunctional assaysTransposon endDNAReceptor geneBase unstackingDomesticationTransposaseRecombinaseAdaptive immunityFinal step
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 Research
2013
Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2
Chan EA, Teng G, Corbett E, Choudhury KR, Bassing CH, Schatz DG, Krangel MS. Peripheral subnuclear positioning suppresses Tcrb recombination and segregates Tcrb alleles from RAG2. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: e4628-e4637. PMID: 24218622, PMCID: PMC3845165, DOI: 10.1073/pnas.1310846110.Peer-Reviewed Original ResearchConceptsTcrb allelesNuclear peripheryNuclear laminaDNA repair protein 53BP1RNA polymerase IIGene 2 proteinHistone H3K4 trimethylationPericentromeric heterochromatinPolymerase IIH3K4 trimethylationRAG proteinsProtein 53BP1Subnuclear distributionRecombination eventsAllelic exclusionDouble-negative thymocytesT-cell receptor β
2012
Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions
Subrahmanyam R, Du H, Ivanova I, Chakraborty T, Ji Y, Zhang Y, Alt FW, Schatz DG, Sen R. Localized epigenetic changes induced by DH recombination restricts recombinase to DJH junctions. Nature Immunology 2012, 13: 1205-1212. PMID: 23104096, PMCID: PMC3685187, DOI: 10.1038/ni.2447.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesCell LineChromatinEpigenesis, GeneticGene Rearrangement, B-Lymphocyte, Heavy ChainGenes, Immunoglobulin Heavy ChainHistonesImmunoglobulin Heavy ChainsImmunoglobulin Joining RegionImmunoglobulin Variable RegionMicePrecursor Cells, B-LymphoidRecombinasesRecombination, Genetic
2011
Recombination 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
2010
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination
Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. Journal Of Experimental Medicine 2010, 207: 2809-2816. PMID: 21115692, PMCID: PMC3005232, DOI: 10.1084/jem.20101136.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding, CompetitiveChromatin ImmunoprecipitationDNAEnhancer Elements, GeneticFemaleGene RearrangementGenes, ImmunoglobulinGenotypeHistonesHMGB1 ProteinHomeodomain ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein BindingReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticTranscription, GeneticVDJ RecombinasesThe In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci
Ji Y, Resch W, Corbett E, Yamane A, Casellas R, Schatz DG. The In Vivo Pattern of Binding of RAG1 and RAG2 to Antigen Receptor Loci. Cell 2010, 141: 419-431. PMID: 20398922, PMCID: PMC2879619, DOI: 10.1016/j.cell.2010.03.010.Peer-Reviewed Original ResearchConceptsJ gene segmentsRAG proteinsGene segmentsSignal sequenceLineage-specific mannerAntigen receptor lociRecombination signal sequencesLysine 4Active chromatinRAG2 bindThousands of sitesHistone 3Receptor locusDevelopmental stagesD gene segmentsDiscrete sitesCritical initial stepVivo patternRAG1BindingRAG2Beta JProteinRecombinationSpecific binding
2009
RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci
Hewitt SL, Yin B, Ji Y, Chaumeil J, Marszalek K, Tenthorey J, Salvagiotto G, Steinel N, Ramsey LB, Ghysdael J, Farrar MA, Sleckman BP, Schatz DG, Busslinger M, Bassing CH, Skok JA. RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin loci. Nature Immunology 2009, 10: 655-664. PMID: 19448632, PMCID: PMC2693356, DOI: 10.1038/ni.1735.Peer-Reviewed Original ResearchAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsB-LymphocytesCell Cycle ProteinsCells, CulturedDNA BreaksDNA-Binding ProteinsGene RearrangementHomeodomain ProteinsImmunoglobulinsMiceMice, Inbred C57BLMice, KnockoutProtein Serine-Threonine KinasesRecombination, GeneticTumor Suppressor ProteinsVDJ Recombinases
2007
The Beyond 12/23 Restriction Is Imposed at the Nicking and Pairing Steps of DNA Cleavage during V(D)J Recombination
Drejer-Teel AH, Fugmann SD, Schatz DG. The Beyond 12/23 Restriction Is Imposed at the Nicking and Pairing Steps of DNA Cleavage during V(D)J Recombination. Molecular And Cellular Biology 2007, 27: 6288-6299. PMID: 17636023, PMCID: PMC2099602, DOI: 10.1128/mcb.00835-07.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesDNA cleavageGene segmentsDNA cleavage stepRecombination-activating gene 1Dbeta gene segmentVariable region exonsJbeta gene segmentsRAG proteinsDNA elementsSignal sequenceDirect VbetaRegion exonsGene 1Oligonucleotide substratesLocus sequenceDistinct combinationsProteinRecombinationCleavageNickingCleavage stepSequenceDifferent stepsExonsFluorescence Resonance Energy Transfer Analysis of Recombination Signal Sequence Configuration in the RAG1/2 Synaptic Complex
Ciubotaru M, Kriatchko AN, Swanson PC, Bright FV, Schatz DG. Fluorescence Resonance Energy Transfer Analysis of Recombination Signal Sequence Configuration in the RAG1/2 Synaptic Complex. Molecular And Cellular Biology 2007, 27: 4745-4758. PMID: 17470556, PMCID: PMC1951485, DOI: 10.1128/mcb.00177-07.Peer-Reviewed Original Research
2005
Biochemistry of V(D)J Recombination
Schatz DG, Spanopoulou E. Biochemistry of V(D)J Recombination. Current Topics In Microbiology And Immunology 2005, 290: 49-85. PMID: 16480039, DOI: 10.1007/3-540-26363-2_4.Peer-Reviewed Original Research
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 ResearchConceptsRecombination 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 substratesHMG1UNGstoppable Switching
Unniraman S, Fugmann SD, Schatz DG. UNGstoppable Switching. Science 2004, 305: 1113-1114. PMID: 15326342, DOI: 10.1126/science.1102692.Peer-Reviewed Original ResearchNew 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 studiesGenomeMutational Analysis of Terminal Deoxynucleotidyltransferase- Mediated N-Nucleotide Addition in V(D)J Recombination
Repasky JA, Corbett E, Boboila C, Schatz DG. Mutational Analysis of Terminal Deoxynucleotidyltransferase- Mediated N-Nucleotide Addition in V(D)J Recombination. The Journal Of Immunology 2004, 172: 5478-5488. PMID: 15100289, DOI: 10.4049/jimmunol.172.9.5478.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibody DiversityCell LineCHO CellsCricetinaeDNA Mutational AnalysisDNA NucleotidylexotransferaseDNA-Binding ProteinsGene RearrangementHomeodomain ProteinsHumansImmunoglobulin Joining RegionImmunoglobulin Variable RegionIsoenzymesMiceNuclear ProteinsNucleotidesOpen Reading FramesPlasmidsRecombination, GeneticSignal TransductionSubstrate SpecificityTemplates, GeneticConceptsNucleotide additionEntire C-terminal regionAg receptor genesProtein-DNA interactionsC-terminal domainStructure-function analysisC-terminal regionN-terminal portionIndividual structural motifsUnique DNA polymeraseBRCT domainHelix domainTdT proteinCatalytic regionDeletional analysisMutational analysisLong isoformNontemplated (N) nucleotidesNucleotide deletionDNA polymeraseDiverse repertoireReceptor geneStructural motifsNonlymphoid cellsCritical roleStaggered AID‐dependent DNA double strand breaks are the predominant DNA lesions targeted to Sµ in Ig class switch recombination
Rush JS, Fugmann SD, Schatz DG. Staggered AID‐dependent DNA double strand breaks are the predominant DNA lesions targeted to Sµ in Ig class switch recombination. International Immunology 2004, 16: 549-557. PMID: 15039385, DOI: 10.1093/intimm/dxh057.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodies, MonoclonalBlotting, SouthernB-LymphocytesCell DivisionCytidine DeaminaseDeoxyribonucleases, Type II Site-SpecificDNADNA DamageDNA PrimersFlow CytometryGene ExpressionImmunoglobulin Class SwitchingImmunoglobulin DImmunoglobulin GImmunoglobulin Switch RegionInterleukin-4LipopolysaccharidesMiceMice, Inbred C57BLMice, KnockoutPlasmidsPolymerase Chain ReactionRecombination, GeneticConceptsClass switch recombinationDNA double-strand breaksPredominant DNA lesionsDouble-strand breaksActivation-induced cytidine deaminaseDNA lesionsSwitch recombinationAID-dependent DNA double-strand breaksStrand breaksIg class switch recombinationLigation-mediated PCRS mu regionCellular regulationKinetics of inductionMolecular detailsMurine B cellsDNA DSBsStaggered breaksCytidine deaminaseDSBsMu regionMinor speciesB cellsS muEffector properties
2003
DNA mismatches and GC‐rich motifs target transposition by the RAG1/RAG2 transposase
Tsai C, Chatterji M, Schatz DG. DNA mismatches and GC‐rich motifs target transposition by the RAG1/RAG2 transposase. Nucleic Acids Research 2003, 31: 6180-6190. PMID: 14576304, PMCID: PMC275461, DOI: 10.1093/nar/gkg819.Peer-Reviewed Original ResearchA Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences
Lee AI, Fugmann SD, Cowell LG, Ptaszek LM, Kelsoe G, Schatz DG. A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences. PLOS Biology 2003, 1: e1. PMID: 14551903, PMCID: PMC212687, DOI: 10.1371/journal.pbio.0000001.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSignal sequenceGene segmentsProtein-DNA interactionsLevel of recombinationDegree of conservationParticular functional importanceJ gene segmentsAntigen receptor genesSpacer variantsRAG proteinsRecombination machineryRSS activityInactive pseudogeneRSS functionSpacer sequencesFunctional analysisInteraction surfaceFunctional importanceLymphocyte developmentNumerous complex interactionsBiochemical assaysDistinct cooperationReceptor geneHeptamerRNA AIDs DNA
Fugmann SD, Schatz DG. RNA AIDs DNA. Nature Immunology 2003, 4: 429-430. PMID: 12719733, DOI: 10.1038/ni0503-429.Peer-Reviewed Original Research