Featured Publications
Transposon 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
2021
Structural visualization of transcription activated by a multidrug-sensing MerR family regulator
Yang Y, Liu C, Zhou W, Shi W, Chen M, Zhang B, Schatz DG, Hu Y, Liu B. Structural visualization of transcription activated by a multidrug-sensing MerR family regulator. Nature Communications 2021, 12: 2702. PMID: 33976201, PMCID: PMC8113463, DOI: 10.1038/s41467-021-22990-8.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsBacterial ProteinsBase SequenceBinding SitesCloning, MolecularCryoelectron MicroscopyCrystallography, X-RayDNA, BacterialDNA-Binding ProteinsDNA-Directed RNA PolymerasesEscherichia coliGene ExpressionGene Expression Regulation, BacterialGenetic VectorsModels, MolecularNucleic Acid ConformationPromoter Regions, GeneticProtein BindingProtein Conformation, alpha-HelicalProtein Conformation, beta-StrandProtein Interaction Domains and MotifsRecombinant ProteinsTranscription Elongation, GeneticTranscription Initiation, GeneticConceptsMerR family regulatorsFamily regulatorCryo-electron microscopy structureBacterial RNA polymerase holoenzymeRegulation of transcriptionRNA polymerase holoenzymePromoter openingTranscription regulationMicroscopy structureTranscription initiationPolymerase holoenzymeRNA elongationTranscriptional regulatorsMerR familyDNA remodelingSpacer DNAPromoter recognitionPromoter elementsCellular signalsSpacer promoterInitial transcriptionTranscription processTranscriptionPromoterRegulator
2015
RAG 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
2014
Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein
Buerstedde JM, Lowndes N, Schatz DG. Induction of homologous recombination between sequence repeats by the activation induced cytidine deaminase (AID) protein. ELife 2014, 3: e03110. PMID: 25006166, PMCID: PMC4080448, DOI: 10.7554/elife.03110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsB-LymphocytesBase SequenceCell LineChickensCrossing Over, GeneticCytidine DeaminaseGene ConversionGenes, ReporterGreen Fluorescent ProteinsHomologous RecombinationHumansImmunoglobulin Switch RegionLuminescent ProteinsMiceModels, GeneticMolecular Sequence DataNucleic Acid HeteroduplexesRecombinational DNA RepairRepetitive Sequences, Nucleic AcidSequence DeletionSequence Homology, Nucleic AcidSomatic Hypermutation, ImmunoglobulinConceptsHomologous recombinationCytidine deaminase proteinSequence repeatsCytidine deaminationDNA end resectionHundreds of basesAnalysis of recombinantsVertebrate cellsGene conversionRepeat recombinationEnd resectionHolliday junctionsHomologous sequencesSequence homologyReporter transgeneStrand invasionIntergenic deletionRecombinogenic activityImmunoglobulin lociRepeatsSomatic hypermutationHeteroduplex formationRecombinationProteinDeamination
2013
The Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements
Steinel NC, Lee BS, Tubbs AT, Bednarski JJ, Schulte E, Yang-Iott KS, Schatz DG, Sleckman BP, Bassing CH. The Ataxia Telangiectasia mutated kinase controls Igκ allelic exclusion by inhibiting secondary Vκ-to-Jκ rearrangements. Journal Of Experimental Medicine 2013, 210: 233-239. PMID: 23382544, PMCID: PMC3570110, DOI: 10.1084/jem.20121605.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsB-LymphocytesBase SequenceCell Cycle ProteinsDNA Breaks, Double-StrandedDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Light ChainHistonesHomeodomain ProteinsImmunoglobulin kappa-ChainsIntracellular Signaling Peptides and ProteinsMiceMice, 129 StrainMice, KnockoutModels, BiologicalProtein Serine-Threonine KinasesRNA, MessengerSignal TransductionTumor Suppressor ProteinsConceptsDNA double-strand breaksRAG DNA double-strand breaksAllelic exclusionIgκ rearrangementAtaxia telangiectasiaProtein kinase kinaseAntigen receptor chainsDouble-strand breaksHistone H2AX phosphorylationFeedback inhibitionATM kinaseIgκ recombinationKinase kinaseDNA-PKConcomitant repressionH2AX phosphorylationRAG endonucleaseReceptor chainsMDC1H2AXKinaseAllelesRecombinationRearrangementTelangiectasia
2009
Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis
Yin FF, Bailey S, Innis CA, Ciubotaru M, Kamtekar S, Steitz TA, Schatz DG. Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsis. Nature Structural & Molecular Biology 2009, 16: 499-508. PMID: 19396172, PMCID: PMC2715281, DOI: 10.1038/nsmb.1593.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAmino Acid SequenceAnimalsBase SequenceChromosome PairingCrystallography, X-RayDNAFluorescence Resonance Energy TransferHomeodomain ProteinsMiceModels, MolecularMolecular Sequence DataNucleic Acid ConformationProtein MultimerizationProtein Structure, QuaternaryProtein Structure, TertiarySolutionsStatic Electricity
2008
Pillars article: the V(D)J recombination activating gene, RAG-1. 1989.
Schatz DG, Oettinger MA, Baltimore D. Pillars article: the V(D)J recombination activating gene, RAG-1. 1989. The Journal Of Immunology 2008, 180: 5-18. PMID: 18096996.Peer-Reviewed Original Research
2007
Strand-Biased Spreading of Mutations During Somatic Hypermutation
Unniraman S, Schatz DG. Strand-Biased Spreading of Mutations During Somatic Hypermutation. Science 2007, 317: 1227-1230. PMID: 17761884, DOI: 10.1126/science.1145065.Peer-Reviewed Original Research
2006
Mobilization of RAG-Generated Signal Ends by Transposition and Insertion In Vivo
Chatterji M, Tsai CL, Schatz DG. Mobilization of RAG-Generated Signal Ends by Transposition and Insertion In Vivo. Molecular And Cellular Biology 2006, 26: 1558-1568. PMID: 16449665, PMCID: PMC1367191, DOI: 10.1128/mcb.26.4.1558-1568.2006.Peer-Reviewed Original ResearchConceptsRAG proteinsVertebrate cellsTransposition eventsEnd fragmentsFull-length RAG2Embryonic kidney cell lineHuman embryonic kidney cell lineTarget site duplicationsGenome instabilityHuman genomeSignal endsKidney cell lineGenomic instabilityTranslocation eventsSite duplicationsChromosomal translocationsDNA cleavageComplex rearrangementsChromosome deletionsEssential roleProteinCell linesEpisomesDeletionAssays
2004
Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc
Unniraman S, Zhou S, Schatz DG. Identification of an AID-independent pathway for chromosomal translocations between the Igh switch region and Myc. Nature Immunology 2004, 5: 1117-1123. PMID: 15489857, DOI: 10.1038/ni1127.Peer-Reviewed Original ResearchB cell–specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5
Johnson K, Pflugh DL, Yu D, Hesslein DG, Lin KI, Bothwell AL, Thomas-Tikhonenko A, Schatz DG, Calame K. B cell–specific loss of histone 3 lysine 9 methylation in the VH locus depends on Pax5. Nature Immunology 2004, 5: 853-861. PMID: 15258579, PMCID: PMC1635547, DOI: 10.1038/ni1099.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceB-LymphocytesCell LineageCells, CulturedDNA-Binding ProteinsFlow CytometryGene Rearrangement, B-LymphocyteHematopoietic Stem CellsHistonesImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionLysineMethylationMiceModels, ImmunologicalMolecular Sequence DataPAX5 Transcription FactorPrecipitin TestsReverse Transcriptase Polymerase Chain ReactionTranscription FactorsConceptsH3-K9 methylationDJH recombinationVH locusHistone 3 lysine 9 methylationLysine 9 methylationFunction of Pax5Non-B lineage cellsB cell-specific lossB cell commitmentHistone exchangeInactive chromatinLysine 9Histone H3Transcription factorsCell commitmentCell-specific lossInhibitory modificationMethylationLineage cellsLociPAX5B cellsHeavy chain rearrangementRecombinationChain rearrangement
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 Research
2002
RAG1-DNA Binding in V(D)J Recombination SPECIFICITY AND DNA-INDUCED CONFORMATIONAL CHANGES REVEALED BY FLUORESCENCE AND CD SPECTROSCOPY*
Ciubotaru M, Ptaszek LM, Baker GA, Baker SN, Bright FV, Schatz DG. RAG1-DNA Binding in V(D)J Recombination SPECIFICITY AND DNA-INDUCED CONFORMATIONAL CHANGES REVEALED BY FLUORESCENCE AND CD SPECTROSCOPY*. Journal Of Biological Chemistry 2002, 278: 5584-5596. PMID: 12488446, DOI: 10.1074/jbc.m209758200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceBinding SitesCircular DichroismCloning, MolecularDNADNA NucleotidyltransferasesDNA-Binding ProteinsEscherichia coliGenes, RAG-1Homeodomain ProteinsKineticsMiceOligodeoxyribonucleotidesProtein ConformationRecombinant ProteinsRecombination, GeneticSubstrate SpecificityTransfectionTransposasesVDJ RecombinasesConceptsRecombination signal sequencesConformational changesSynaptic complex formationAbsence of DNAAssembly of immunoglobulinMajor conformational changesIntrinsic protein fluorophoresProtein intrinsic fluorescenceSolvent-exposed environmentRAG2 proteinsRAG1/2 complexSingle DNA moleculesRAG1 proteinSignal sequenceAcrylamide quenching studiesT-cell receptor genesStrep-tagRecombination specificityDNA moleculesProtein fluorophoresRAG1Receptor geneProteinIntrinsic fluorescenceCircular dichroism
2000
Genetic Modulation of T Cell Receptor Gene Segment Usage during Somatic Recombination
Livak F, Burtrum D, Rowen L, Schatz D, Petrie H. Genetic Modulation of T Cell Receptor Gene Segment Usage during Somatic Recombination. Journal Of Experimental Medicine 2000, 192: 1191-1196. PMID: 11034609, PMCID: PMC2195867, DOI: 10.1084/jem.192.8.1191.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesFlanking recombination signal sequencesGene segment usageUseful gene productsLymphocyte antigen receptorsSegment usageSignal sequenceSomatic cellsCombinatorial joiningGene productsSomatic recombinationRecombinase activityGenetic modulationGene segmentsBeta gene segment usageMature T lymphocytesD betaSynaptic complexGermline genesTotal repertoireNaive repertoireAntigen receptorRecombinationRepertoireBiased representation
1999
A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2
Rodgers K, Villey I, Ptaszek L, Corbett E, Schatz D, Coleman J. A dimer of the lymphoid protein RAG1 recognizes the recombination signal sequence and the complex stably incorporates the high mobility group protein HMG2. Nucleic Acids Research 1999, 27: 2938-2946. PMID: 10390537, PMCID: PMC148510, DOI: 10.1093/nar/27.14.2938.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSignal sequenceCore RAG1RAG1/RAG2 complexAbsence of RAG2Lymphoid-specific proteinsElectrophoretic mobility shift assaysSingle recombination signal sequencesMobility shift assaysRAG1 proteinProteins RAG1DNA sequencesMinimal speciesShift assaysOligomeric complexesHeptamer sequenceCompetition assaysRAG1Escherichia coliOligomeric formsRAG2Cleavage activityHMG2ProteinJ region[19] cDNA representational difference analysis: A sensitive and flexible method for identification of differentially expressed genes
Hubank M, Schatz DG. [19] cDNA representational difference analysis: A sensitive and flexible method for identification of differentially expressed genes. Methods In Enzymology 1999, 303: 325-349. PMID: 10349653, DOI: 10.1016/s0076-6879(99)03021-9.Peer-Reviewed Original Research
1997
V(D)J recombination movesin vitro
Schatz D. V(D)J recombination movesin vitro. Seminars In Immunology 1997, 9: 149-159. PMID: 9200326, DOI: 10.1006/smim.1997.0068.Commentaries, Editorials and Letters
1996
Transient restoration of gene rearrangement at multiple T cell receptor loci in gamma-irradiated scid mice.
Livák F, Welsh SC, Guidos CJ, Crispe IN, Danska JS, Schatz DG. Transient restoration of gene rearrangement at multiple T cell receptor loci in gamma-irradiated scid mice. Journal Of Experimental Medicine 1996, 184: 419-428. PMID: 8760795, PMCID: PMC2192694, DOI: 10.1084/jem.184.2.419.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnimals, NewbornBase SequenceFemaleGamma RaysGene Rearrangement, alpha-Chain T-Cell Antigen ReceptorGene Rearrangement, delta-Chain T-Cell Antigen ReceptorMaleMiceMice, Inbred AKRMice, Inbred BALB CMice, Inbred C57BLMice, SCIDMolecular Sequence DataReceptors, Antigen, T-CellRecombination, GeneticRestriction MappingThymus GlandA Zinc-binding Domain Involved in the Dimerization of RAG1
Rodgers K, Bu Z, Fleming K, Schatz D, Engelman D, Coleman J. A Zinc-binding Domain Involved in the Dimerization of RAG1. Journal Of Molecular Biology 1996, 260: 70-84. PMID: 8676393, DOI: 10.1006/jmbi.1996.0382.Peer-Reviewed Original ResearchConceptsRecombination-activating gene 1Zinc-binding motifDimerization domainZinc fingerProtein-protein interactionsLymphoid-specific genesN-terminal thirdZinc finger sequencesAmino acid residuesC3HC4 motifRAG1 sequencesRAG1 proteinTerminal domainHomodimer formationAcid residuesBiophysical techniquesGene 1Energetics of associationMonomeric subunitsMotifProteinFinger sequencesSequenceC3HC4Zinc ions