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 eventRecombinationCleavageVertebrates
2015
Single-molecule analysis of RAG-mediated V(D)J DNA cleavage
Lovely GA, Brewster RC, Schatz DG, Baltimore D, Phillips R. Single-molecule analysis of RAG-mediated V(D)J DNA cleavage. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: e1715-e1723. PMID: 25831509, PMCID: PMC4394307, DOI: 10.1073/pnas.1503477112.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSingle-molecule assaysSame DNA moleculeAntigen receptor genesConsensus recombination signal sequencesSingle-molecule analysisHigh mobility group box protein 1Individual molecular eventsSignal sequenceSingle-molecule levelGene productsDNA bindingMolecular eventsLymphocyte developmentDNA moleculesDNA cleavageProtein 1Synapse formationSynaptic complexReceptor geneCleavageRAGAssaysRAG1/2Complexes
2013
Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers
Chaumeil J, Micsinai M, Ntziachristos P, Deriano L, Wang J, Ji Y, Nora EP, Rodesch MJ, Jeddeloh JA, Aifantis I, Kluger Y, Schatz DG, Skok JA. Higher-Order Looping and Nuclear Organization of Tcra Facilitate Targeted RAG Cleavage and Regulated Rearrangement in Recombination Centers. Cell Reports 2013, 3: 359-370. PMID: 23416051, PMCID: PMC3664546, DOI: 10.1016/j.celrep.2013.01.024.Peer-Reviewed Original ResearchMeSH KeywordsAllelesAnimalsAtaxia Telangiectasia Mutated ProteinsCell Cycle ProteinsCell NucleusDNA DamageDNA-Binding ProteinsGenetic LociGenomic InstabilityHistonesHomeodomain ProteinsMiceMice, Inbred C57BLMice, Inbred CBAMice, KnockoutProtein Serine-Threonine KinasesReceptors, Antigen, T-Cell, alpha-betaTumor Suppressor ProteinsV(D)J RecombinationConceptsAntigen receptor lociRegulated rearrangementsGenome stabilityNuclear organizationRAG cleavageRAG recombinaseNuclear accessibilityRAG bindingCellular transformationΑ locusRecombination eventsReceptor locusDiverse arrayCell receptorLociLoop formationTight controlRegulationCleavageFocal bindingGenetic anomaliesBindingKey determinantRearrangementTranscription
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
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 stepsExons
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 substratesHMG1
1999
Detection of RAG Protein-V(D)J Recombination Signal Interactions Near the Site of DNA Cleavage by UV Cross-Linking
Eastman Q, Villey I, Schatz D. Detection of RAG Protein-V(D)J Recombination Signal Interactions Near the Site of DNA Cleavage by UV Cross-Linking. Molecular And Cellular Biology 1999, 19: 3788-3797. PMID: 10207102, PMCID: PMC84213, DOI: 10.1128/mcb.19.5.3788.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesRAG proteinsRAG2 proteinsDNA cleavageHeptamer elementSite of cleavageActive site organizationRAG1-RAG2RAG1 proteinSignal sequenceDouble-strand cleavageSite-specific interactionsSame nucleotideRecognition surfaceProteinRAG1UV CrossSignal interactionsSite organizationCleavageSequenceComplexesSitesClose proximityNucleotides
1997
Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage
Eastman Q, Schatz D. Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage. Nucleic Acids Research 1997, 25: 4370-4378. PMID: 9336470, PMCID: PMC147051, DOI: 10.1093/nar/25.21.4370.Peer-Reviewed Original ResearchRAG1 and RAG2 Form a Stable Postcleavage Synaptic Complex with DNA Containing Signal Ends in V(D)J Recombination
Agrawal A, Schatz D. RAG1 and RAG2 Form a Stable Postcleavage Synaptic Complex with DNA Containing Signal Ends in V(D)J Recombination. Cell 1997, 89: 43-53. PMID: 9094713, DOI: 10.1016/s0092-8674(00)80181-6.Peer-Reviewed Original ResearchConceptsSignal endsRecombination signalsDNA-dependent protein kinaseProtein-DNA complexesSynaptic complexHMG-2 proteinStable complexesDNA adjacentProtein kinaseProteins RAG1Immunoprecipitation experimentsMobility shiftNuclease sensitivityHMG-1Cleavage systemRAG1RAG2RecombinationComplexesVivo observationsKinaseProteinImportant stepCleavage
1996
RAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination
Difilippantonio M, McMahan C, Eastman Q, Spanopoulou E, Schatz D. RAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination. Cell 1996, 87: 253-262. PMID: 8861909, DOI: 10.1016/s0092-8674(00)81343-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell LineDNA NucleotidyltransferasesDNA-Binding ProteinsGenes, ImmunoglobulinHomeodomain ProteinsHumansMacromolecular SubstancesMolecular Sequence DataNuclear ProteinsProtein BindingProteinsRecombinant ProteinsRecombination, GeneticSalmonellaSequence AlignmentStructure-Activity RelationshipTranscriptional ActivationTransfectionConceptsDNA bindingAbsence of RAG2Signal sequence recognitionRegion of RAG1RAG2 proteinsBacterial invertasesSequence similarityRecombination signalsSpecific binding interactionsRAG1Sequence recognitionDNA cleavageRAG2Binding interactionsProteinBindingRecombinationRecent studiesSignal recognitionInvertaseHeptamerRecruitmentCleavageLocalizationVivoInitiation of V(D)J recombination in vitro obeying the 12/23 rule
Eastman Q, Leu T, Schatz D. Initiation of V(D)J recombination in vitro obeying the 12/23 rule. Nature 1996, 380: 85-88. PMID: 8598914, DOI: 10.1038/380085a0.Peer-Reviewed Original Research