2014
Targeting Of Somatic Hypermutation By immunoglobulin Enhancer And Enhancer-Like Sequences
Buerstedde JM, Alinikula J, Arakawa H, McDonald JJ, Schatz DG. Targeting Of Somatic Hypermutation By immunoglobulin Enhancer And Enhancer-Like Sequences. PLOS Biology 2014, 12: e1001831. PMID: 24691034, PMCID: PMC3972084, DOI: 10.1371/journal.pbio.1001831.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAntibodiesBinding SitesB-LymphocytesCell LineChickensCytidine DeaminaseE-Box ElementsEnhancer Elements, GeneticGene Knockout TechniquesGreen Fluorescent ProteinsHumansImmunoglobulin kappa-ChainsImmunoglobulin lambda-ChainsLymphocyte ActivationMEF2 Transcription FactorsMiceMutationNF-kappa BSequence AlignmentSomatic Hypermutation, ImmunoglobulinTranscription, GeneticUracil-DNA GlycosidaseConceptsSomatic hypermutationIg enhancersNovel regulatory functionStimulation of transcriptionEnhancer-like elementCytidine deaminase proteinEnhancer-like sequenceActivation-induced cytidine deaminase proteinGene specificityTranscriptional roleHeavy chain intron enhancerTranscription unitGenetic diversityEts familyE-boxChicken cellsRegulatory functionsIntron enhancerFull activationImmunoglobulin genesTarget sequenceImmunoglobulin enhancerPoint mutationsEnhancerTranscription
2012
AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells
Gramlich HS, Reisbig T, Schatz DG. AID-Targeting and Hypermutation of Non-Immunoglobulin Genes Does Not Correlate with Proximity to Immunoglobulin Genes in Germinal Center B Cells. PLOS ONE 2012, 7: e39601. PMID: 22768095, PMCID: PMC3387148, DOI: 10.1371/journal.pone.0039601.Peer-Reviewed Original ResearchConceptsNon-Ig genesC-MycIg genesAID targetingGerminal center B cellsDouble-strand break endsImportant regulatory elementsNon-immunoglobulin genesMYC transgeneHeavy chain geneRegulatory elementsBreak endsIg heavy chain genesIg lociHuman MYCGenesB cellsSuch translocationsImmunoglobulin lociImmunoglobulin genesTranslocation partnersChain geneHuman Burkitt lymphomaSomatic hypermutationNuclear position
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 GlycosidaseConceptsImmunoglobulin genesCytidine deaminase AIDUracil residuesGenesCell stimulationGene variablesB cell stimulationResiduesUracil
2008
Two levels of protection for the B cell genome during somatic hypermutation
Liu M, Duke JL, Richter DJ, Vinuesa CG, Goodnow CC, Kleinstein SH, Schatz DG. Two levels of protection for the B cell genome during somatic hypermutation. Nature 2008, 451: 841-845. PMID: 18273020, DOI: 10.1038/nature06547.Peer-Reviewed Original ResearchConceptsError-free DNA repairB cell genomeGenomic stabilityNumerous oncogenesDNA repairCell genomeBase excisionGenomeMismatch repairImmunoglobulin genesSomatic hypermutationWidespread mutationsHypermutationB-cell tumorsB-cell malignanciesHigh-affinity antibodiesB cellsGenesOncogeneLarge fractionDiversityVital roleMutationsEnzymeRepair
2007
Targeting of AID‐Mediated Sequence Diversification by cis‐Acting Determinants
Yang SY, Schatz DG. Targeting of AID‐Mediated Sequence Diversification by cis‐Acting Determinants. Advances In Immunology 2007, 94: 109-125. PMID: 17560273, DOI: 10.1016/s0065-2776(06)94004-8.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseSequence diversificationFeatures of chromatinTranscriptional control elementsCis-acting determinantsClass switch recombinationGene conversionDiversification processMolecular mechanismsIg lociSwitch recombinationIg genesAntibody diversityImmunoglobulin genesCytidine deaminaseSomatic hypermutationControl elementsTranscriptionGenesDiversificationRecombinationChromatinLociDiversityPermissive
2004
Non‐redundancy of cytidine deaminases in class switch recombination
Fugmann SD, Rush JS, Schatz DG. Non‐redundancy of cytidine deaminases in class switch recombination. European Journal Of Immunology 2004, 34: 844-849. PMID: 14991614, DOI: 10.1002/eji.200324418.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseClass switch recombinationAPOBEC-1Human activation-induced cytidine deaminaseSwitch recombinationCognate substratesCatalytic mutantGene conversionClose homologueProkaryotic cellsInactive mutantMurine B cellsDistinct mRNAsCytidine deaminase activityCytidine deaminasesImmunoglobulin genesDiversification mechanismsCytidine deaminaseSomatic hypermutationUnknown mechanismDeaminase activityMutantsPrecise roleActivated B cellsB cells
2002
The Activation-induced Deaminase Functions in a Postcleavage Step of the Somatic Hypermutation Process
Papavasiliou FN, Schatz DG. The Activation-induced Deaminase Functions in a Postcleavage Step of the Somatic Hypermutation Process. Journal Of Experimental Medicine 2002, 195: 1193-1198. PMID: 11994424, PMCID: PMC2193708, DOI: 10.1084/jem.20011858.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseClass switch recombinationSomatic hypermutationDNA lesionsDownstream constant region genesCytidine deaminase motifDominant-negative formConstant region genesInitial DNA lesionsSomatic hypermutation processHeavy chain constant regionIg genesNegative formImmunoglobulin genesChain constant regionTarget sequencePoint mutationsCytidine deaminaseHypermutation processGenesAID functionRegion genesMechanistic overlapVariable regionsConstant region
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
1995
Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement
Grawunder U, Leu T, Schatz D, Werner A, Rolink A, Melchers F, Winkler T. Down-regulation of RAG1 and RAG2 gene expression in PreB cells after functional immunoglobulin heavy chain rearrangement. Immunity 1995, 3: 601-608. PMID: 7584150, DOI: 10.1016/1074-7613(95)90131-0.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBase SequenceB-LymphocytesCell DifferentiationCell LineDNA-Binding ProteinsDown-RegulationFemaleFlow CytometryGene Rearrangement, B-LymphocyteHomeodomain ProteinsImmunoglobulin Heavy ChainsMiceMice, Inbred C57BLMice, Inbred DBAMice, Inbred StrainsMolecular Sequence DataPolymerase Chain ReactionProtein BiosynthesisProteinsProto-Oncogene Proteins c-kitReceptors, Antigen, B-CellRNA, MessengerConceptsRAG2 gene expressionPreB cellsGene expressionFunctional immunoglobulin genesPreB-II cellsPreB cell receptorB cell developmentCell cycle statusHeavy chain allelesRAG2 proteinsPostranscriptional levelImmature B cellsRAG genesGene productsTranscriptional levelProductive rearrangementsMouse bone marrowCell developmentDifferential surface expressionImmunoglobulin genesRAG1Cell surfaceRAG2 mRNAGenesCycle status
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 Research
1987
Increased Frequency of N-Region Insertion in a Murine Pre-B-Cell Line Infected with a Terminal Deoxynucleotidyl Transferase Retroviral Expression Vector
Landau N, Schatz D, 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. DOI: 10.1128/mcb.7.9.3237-3243.1987.Peer-Reviewed Original ResearchPre-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 regionInsertionIncreased 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 regionInsertionIncreased Frequency of N-Region Insertion in a Murine Pre-B-Cell Line Infected with a Terminal Deoxynucleotidyl Transferase Retroviral Expression Vector
Landau N, Schatz D, 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. DOI: 10.1128/mcb.7.9.3237-3243.1987.Peer-Reviewed Original ResearchPre-B-cell lineN-region insertionsCell linesExpression vectorRetroviral expression vectorImmunoglobulin light chain genesNucleotide sequence analysisV-J junctionLight chain genesGene junctionPre-B-cellSequence analysisMurine pre-B-cell lineTerminal deoxynucleotidyl transferaseRearranged genesImmunoglobulin genesJunction sitesN regionRearranged provirusesPresence of TdTGenesInfected cellsRearrangement substratesDeoxynucleotidyl transferaseNucleotide