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 ResearchNucleolar localization of RAG1 modulates V(D)J recombination activity
Brecht RM, Liu CC, Beilinson HA, Khitun A, Slavoff SA, Schatz DG. Nucleolar localization of RAG1 modulates V(D)J recombination activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 4300-4309. PMID: 32047031, PMCID: PMC7049140, DOI: 10.1073/pnas.1920021117.Peer-Reviewed Original ResearchConceptsNucleolar localizationProximity-dependent biotin identificationRecombination activityDisruption of nucleoliDiscrete gene segmentsAntigen receptor lociPre-B cell linesNegative regulatory mechanismsN-terminal regionAmino acids 216Biotin identificationLocalization motifNucleolar associationProtein complexesNucleolar proteinsNucleolar sequestrationT-cell receptor genesRegulatory mechanismsNucleolar markerReceptor locusEfficient egressRAG1Amino acidsGene segmentsReceptor gene
2019
Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire
Shinoda K, Maman Y, Canela A, Schatz DG, Livak F, Nussenzweig A. Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire. Cell Reports 2019, 29: 4471-4481.e6. PMID: 31875554, PMCID: PMC8214342, DOI: 10.1016/j.celrep.2019.11.088.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksRecombination signal sequencesVκ gene segmentsGene segmentsDouble-strand breaksVariable gene segmentsRAG proteinsSignal sequenceV-J rearrangementRecombination eventsSpacer regionVκ-JκRecombinationLevels of breakageComplete absenceProteinLarge fractionDeletionJκSequence
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
The Role of RAG in V(D)J Recombination
Carmona L, Schatz D. The Role of RAG in V(D)J Recombination. 2016, 99-106. DOI: 10.1016/b978-0-12-374279-7.05012-8.Peer-Reviewed Original ResearchRecombination signal sequencesTransposable elementsCell cycle-dependent mannerAntigen receptor gene segmentsLymphoid-specific proteinsDNA cleavageCycle-dependent mannerReceptor gene segmentsRAG cleavageRAG proteinsTranslational regulationPosttranslational modificationsSignal sequenceNonhomologous endRAG activitySequence elementsEnhancer elementsTransposition mechanismCell cycleLymphocyte developmentGene segmentsPair of hairpinsBlunt endsRecombinationRAG2
2015
Recruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination
Shetty K, Schatz DG. Recruitment of RAG1 and RAG2 to Chromatinized DNA during V(D)J Recombination. Molecular And Cellular Biology 2015, 35: 3701-3713. PMID: 26303526, PMCID: PMC4589606, DOI: 10.1128/mcb.00219-15.Peer-Reviewed Original ResearchConceptsConserved heptamerRAG2 proteinsChromatin immunoprecipitationNonamer elementsRecombination substratesSignal sequenceNonamer sequencesMutant formsCryptic RSSsRAG1DNA cleavageGene segmentsChromatinCell linesRAG2ProteinRecruitmentRecombinationSequenceMajor roleMutagenesisImmunoprecipitationRepeatsRSSsRAG
2011
V(D)J Recombination: Mechanisms of Initiation
Schatz DG, Swanson PC. V(D)J Recombination: Mechanisms of Initiation. Annual Review Of Genetics 2011, 45: 167-202. PMID: 21854230, DOI: 10.1146/annurev-genet-110410-132552.Peer-Reviewed Original ResearchConceptsProtein-DNA complexesUbiquitin ligase activityHistone recognitionDomain organizationRAG proteinsRAG2 proteinsLigase activityT-cell receptor genesRecombination signalsDNA breaksHeptamer sequenceLymphocyte developmentDNA breakageDNA cleavageGene segmentsFunctional significanceProper repairReceptor geneRAG1ProteinRecombinationMechanism of initiationComplexesRecent advancesGenes
2010
The 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
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
2003
A 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 geneHeptamer
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
Transposition mediated by RAG1 and RAG2 and the evolution of the adaptive immune system
Schatz D. Transposition mediated by RAG1 and RAG2 and the evolution of the adaptive immune system. Immunologic Research 1999, 19: 169-182. PMID: 10493171, DOI: 10.1007/bf02786485.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsTransposable elementsAncestral receptor geneAdaptive immune systemReceptor gene segmentsReceptor geneAntigen receptor genesRAG proteinsRAG2 proteinsChromosomal DNAFunctional transposaseMillion yearsGene segmentsRAG1Dramatic supportImmune systemGenesRecent findingsUnusual structureProteinVertebratesTransposaseRAG2DNAEvolutionRecombination
1998
Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system
Agrawal A, Eastman Q, Schatz D. Transposition mediated by RAG1 and RAG2 and its implications for the evolution of the immune system. Nature 1998, 394: 744-751. PMID: 9723614, DOI: 10.1038/29457.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodiesB-LymphocytesBinding SitesCatalysisCell LineDNADNA Transposable ElementsDNA-Binding ProteinsDNA, CircularDrug Resistance, MicrobialEvolution, MolecularGene Rearrangement, B-LymphocyteGene Rearrangement, T-LymphocyteHigh Mobility Group ProteinsHomeodomain ProteinsImmune SystemMiceMolecular Sequence DataReceptors, Antigen, T-CellRecombination, GeneticRestriction MappingTransposasesVertebratesConceptsT-cell receptor genesRecombination signalsSequence-specific DNA recognitionAncestral receptor geneComponent gene segmentsSite-specific recombination reactionPiece of DNAEvolutionary divergenceJawless vertebratesRecombination-activating geneTransposable elementsDNA recognitionRetroviral integrationGermline insertionDNA moleculesGenesShort duplicationsDNA cleavageRAG1Gene segmentsTransposition reactionRAG2Receptor geneTarget DNA moleculesTarget DNA
1997
Identification of V(D)J recombination coding end intermediates in normal thymocytes 11Edited by K. Yamamoto
Livák F, Schatz D. Identification of V(D)J recombination coding end intermediates in normal thymocytes 11Edited by K. Yamamoto. Journal Of Molecular Biology 1997, 267: 1-9. PMID: 9096202, DOI: 10.1006/jmbi.1996.0834.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesNormal lymphoid precursorsSignal endsJ alpha genesPre-B cell linesGene rearrangement processDouble-strand breaksNormal murine thymocytesSignal sequenceLymphoid precursorsK. YamamotoAlpha geneFirst direct demonstrationHairpin structureLow abundanceStrand breaksGene segmentsCell linesAntigen receptorMurine thymocytesRecombinationDirect demonstrationVivoJoint formationNormal thymocytes
1996
The half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression.
Grawunder U, Schatz DG, Leu TM, Rolink A, Melchers F. The half-life of RAG-1 protein in precursor B cells is increased in the absence of RAG-2 expression. Journal Of Experimental Medicine 1996, 183: 1731-1737. PMID: 8666930, PMCID: PMC2192496, DOI: 10.1084/jem.183.4.1731.Peer-Reviewed Original Research