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
2018
DNA melting initiates the RAG catalytic pathway
Ru H, Mi W, Zhang P, Alt FW, Schatz DG, Liao M, Wu H. DNA melting initiates the RAG catalytic pathway. Nature Structural & Molecular Biology 2018, 25: 732-742. PMID: 30061602, PMCID: PMC6080600, DOI: 10.1038/s41594-018-0098-5.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesDNA meltingCryo-EM structureBase-specific contactsSignal sequenceDNA transpositionSubstrate bindingRetroviral integrationRAG endonucleaseDimer openingTerminal sequenceGTG sequenceDNA cleavageScissile phosphateDNAUniversal mechanismPiston-like movementSequenceActive siteHeptamerRetrotransposonsCatalytic pathwayTransposonComplexesEndonuclease
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
2013
A Critical Context-Dependent Role for E Boxes in the Targeting of Somatic Hypermutation
McDonald JJ, Alinikula J, Buerstedde JM, Schatz DG. A Critical Context-Dependent Role for E Boxes in the Targeting of Somatic Hypermutation. The Journal Of Immunology 2013, 191: 1556-1566. PMID: 23836058, PMCID: PMC3735716, DOI: 10.4049/jimmunol.1300969.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBinding SitesB-LymphocytesCells, CulturedChickensCytidine DeaminaseDNA, RecombinantE-Box ElementsEnhancer Elements, GeneticGenes, Immunoglobulin Light ChainGenes, ReporterGreen Fluorescent ProteinsImmunoglobulin Variable RegionMutationProtein BindingSomatic Hypermutation, ImmunoglobulinTranscription Factor 3TransfectionTransgenesConceptsE-boxSomatic hypermutationChicken DT40 B cellsDT40 B cellsNon-Ig lociOff-target mutationsActivation-induced cytidine deaminaseContext-dependent roleShort DNA sequencesSequence motifsDNA sequencesTarget genesIg genesSequence contextAffinity of AbsDNA damageCytidine deaminaseRepertoire diversificationMutationsGenesMotifSequenceFunctional hierarchyHypermutationAg stimulation
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
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
2001
Identification of Basic Residues in RAG2 Critical for DNA Binding by the RAG1-RAG2 Complex
Fugmann S, Schatz D. Identification of Basic Residues in RAG2 Critical for DNA Binding by the RAG1-RAG2 Complex. Molecular Cell 2001, 8: 899-910. PMID: 11684024, DOI: 10.1016/s1097-2765(01)00352-5.Peer-Reviewed Original ResearchConceptsDNA bindingRAG2 proteinsCognate DNA target sequenceDNA target sequencesResidue mutantsMolecular roleBasic residuesDNA cleavageTarget sequenceRAG1Biochemical analysisRAG2BindingCentral roleProteinRecombinationResiduesDirect involvementEssential componentComplexesMutantsCleavage reactionIdentificationRoleSequence
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
1996
A 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 ionsInitiation 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
1990
RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination
Oettinger M, Schatz D, Gorka C, Baltimore D. RAG-1 and RAG-2, Adjacent Genes That Synergistically Activate V(D)J Recombination. Science 1990, 248: 1517-1523. PMID: 2360047, DOI: 10.1126/science.2360047.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceBiological EvolutionCattleCell LineChickensCricetinaeDNADNA NucleotidyltransferasesDNA-Binding ProteinsDogsFemaleGene Rearrangement, B-LymphocyteGene Rearrangement, T-LymphocyteHomeodomain ProteinsHumansMaleMiceMolecular Sequence DataMultigene FamilyNuclear ProteinsNucleic Acid HybridizationOpossumsProteinsRabbitsRecombination, GeneticRestriction MappingTransfectionTurtlesVDJ RecombinasesConceptsRAG-2RAG-1Adjacent genesRecombinase activityFrequency of recombinationPutative proteinUntranslated sequenceSingle exonGenomic rearrangementsExpression patternsVast repertoireGenesComplementary DNAAmino acidsT cell receptorCell receptorRecombinationSequenceKilobasesExonsCotransfectionRecombinaseSpeciesProteinDNA