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
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 KeywordsAnimalsB-LymphocytesBinding SitesCells, 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
2012
Identification of Core DNA Elements That Target Somatic Hypermutation
Kohler KM, McDonald JJ, Duke JL, Arakawa H, Tan S, Kleinstein SH, Buerstedde JM, Schatz DG. Identification of Core DNA Elements That Target Somatic Hypermutation. The Journal Of Immunology 2012, 189: 5314-5326. PMID: 23087403, PMCID: PMC3664039, DOI: 10.4049/jimmunol.1202082.Peer-Reviewed Original ResearchMeSH Keywords3' Flanking RegionAnimalsB-LymphocytesCells, CulturedChickensChromatin ImmunoprecipitationCytidine DeaminaseDNAEnhancer Elements, GeneticGenes, ImmunoglobulinGenetic LociImmunoassayImmunoglobulin Variable RegionMutationPhosphorylationRNA Polymerase IISerineSomatic Hypermutation, ImmunoglobulinTranscription, GeneticConceptsActivation-induced deaminaseDNA elementsSomatic hypermutationChicken DT40 B cellsIg lociChromatin immunoprecipitation experimentsDT40 B cellsRNA polymerase IISystematic deletion analysisL chain lociNon-Ig genesCore DNA elementSerine 5Epigenetic marksPolymerase IITranscriptional elongationMutational machineryDeletion analysisReporter cassetteImmunoprecipitation experimentsDeoxycytosine residuesIg genesDNA damageChain locusLociLocalized 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
2010
Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions
Maul RW, Saribasak H, Martomo SA, McClure RL, Yang W, Vaisman A, Gramlich HS, Schatz DG, Woodgate R, Wilson DM, Gearhart PJ. Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions. Nature Immunology 2010, 12: 70-76. PMID: 21151102, PMCID: PMC3653439, DOI: 10.1038/ni.1970.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntigenic VariationB-LymphocytesCells, CulturedCytidine DeaminaseDNA-(Apurinic or Apyrimidinic Site) LyaseImmunoglobulin Class SwitchingImmunoglobulin Variable RegionInterleukin-4LipopolysaccharidesLymphocyte ActivationMiceMice, Inbred C57BLMice, KnockoutModels, ChemicalSpleenUracilUracil-DNA Glycosidase
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
2004
B 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 rearrangementMutational 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 role
2003
Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments
Hesslein DG, Pflugh DL, Chowdhury D, Bothwell AL, Sen R, Schatz DG. Pax5 is required for recombination of transcribed, acetylated, 5′ IgH V gene segments. Genes & Development 2003, 17: 37-42. PMID: 12514097, PMCID: PMC195966, DOI: 10.1101/gad.1031403.Peer-Reviewed Original ResearchAcetylationAllelesAnimalsB-LymphocytesChromatinDNA NucleotidyltransferasesDNA-Binding ProteinsGene Rearrangement, B-Lymphocyte, Heavy ChainGenes, ImmunoglobulinGenes, RAG-1HistonesHomeodomain ProteinsImmunoglobulin Heavy ChainsImmunoglobulin Variable RegionMiceMice, Inbred C57BLMice, KnockoutPAX5 Transcription FactorTranscription FactorsTranscription, GeneticVDJ Recombinases
2001
Factors and Forces Controlling V(D)J Recombination
Hesslein D, Schatz D. Factors and Forces Controlling V(D)J Recombination. Advances In Immunology 2001, 78: 169-232. PMID: 11432204, DOI: 10.1016/s0065-2776(01)78004-2.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus Statements
2000
Cell-cycle-regulated DNA double-strand breaks in somatic hypermutation of immunoglobulin genes
Papavasiliou F, Schatz D. Cell-cycle-regulated DNA double-strand breaks in somatic hypermutation of immunoglobulin genes. Nature 2000, 408: 216-221. PMID: 11089977, DOI: 10.1038/35041599.Peer-Reviewed Original ResearchConceptsDNA double-strand breaksDouble-strand breaksSomatic hypermutationRepair of DSBsVariable region promotersImmunoglobulin variable region genesDNA replicationHomologous recombinationHeterologous promoterSpecific residuesVariable genesNearby mutationsRegion promoterVariable region genesImmunoglobulin genesHeterologous sequencesChromosomal translocationsPoint mutationsGenesRegion genesMutationsHypermutationTranscriptionPromoterB-cell tumors
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 ResearchMeSH KeywordsAnimalsDNA RepairGene RearrangementImmunoglobulin Joining RegionImmunoglobulin Variable RegionMiceMice, SCIDProtein Sorting SignalsRecombination, GeneticThymus GlandConceptsRecombination 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
1988
Stable expression of immunoglobulin gene V(D)J recombinase activity by gene transfer into 3T3 fibroblasts
Schatz D, Baltimore D. Stable expression of immunoglobulin gene V(D)J recombinase activity by gene transfer into 3T3 fibroblasts. Cell 1988, 53: 107-115. PMID: 3349523, DOI: 10.1016/0092-8674(88)90492-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceCells, CulturedDNA NucleotidyltransferasesGenes, ImmunoglobulinImmunoglobulin Joining RegionImmunoglobulin Variable RegionMiceNucleic Acid HybridizationTransfectionVDJ Recombinases
1987
Increased frequency of N-region insertion in a murine pre-B-cell line infected with a terminal deoxynucleotidyl transferase retroviral expression vector.
Landau NR, Schatz DG, Rosa M, Baltimore D. Increased frequency of N-region insertion in a murine pre-B-cell line infected with a terminal deoxynucleotidyl transferase retroviral expression vector. Molecular And Cellular Biology 1987, 7: 3237-3243. PMID: 3118194, PMCID: PMC367960, DOI: 10.1128/mcb.7.9.3237.Peer-Reviewed Original ResearchConceptsPre-B cell linesN-region insertionsRetroviral expression vectorExpression vectorCell linesMurine pre-B cell lineImmunoglobulin light chain genesNucleotide sequence analysisLight chain genesV-J junctionGene junctionSequence analysisImmunoglobulin genesGenesRearrangement substratesTerminal deoxynucleotidyl transferaseContinuous rearrangementApparent absenceJunctional sitesProvirusDeoxynucleotidyl transferaseRearrangementControl vectorN regionInsertion