2022
Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences.
Tarsalainen A, Maman Y, Meng FL, Kyläniemi MK, Soikkeli A, Budzyńska P, McDonald JJ, Šenigl F, Alt FW, Schatz DG, Alinikula J. Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences. The Journal Of Immunology 2022, 208: 143-154. PMID: 34862258, PMCID: PMC8702490, DOI: 10.4049/jimmunol.2100923.Peer-Reviewed Original ResearchConceptsPol IIMutating geneSomatic hypermutationTarget genesChicken DT40 B cellsRNA polymerase II stallingIg genesHistone variant H3.3Locus-specific targetingPol II occupancyAID-mediated mutationsDT40 B cellsRNA polymerase IILevels of H3K27acFull-length transcriptsVariant H3.3Antisense transcriptionTranscriptional outputPolymerase IIGenetic diversityMechanistic basisBurkitt's lymphoma cellsGeneration of AbsGenesDIVAC
2016
Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination
Carmona LM, Fugmann SD, Schatz DG. Collaboration of RAG2 with RAG1-like proteins during the evolution of V(D)J recombination. Genes & Development 2016, 30: 909-917. PMID: 27056670, PMCID: PMC4840297, DOI: 10.1101/gad.278432.116.Peer-Reviewed Original ResearchConceptsRecombination-activating gene 1Transib transposaseAbsence of RAG2RAG1/RAG2Antigen receptor genesJawed vertebratesRAG2 proteinsTransposable elementsRAG1 proteinRegulatory featuresDNA substratesGene 1RAG2Receptor geneRecombination activityProteinRecombinationTransposaseAdaptive immunityVertebratesTransposonGenesEvolutionLow levelsOrigin
2015
Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes
Hu J, Zhang Y, Zhao L, Frock RL, Du Z, Meyers RM, Meng FL, Schatz DG, Alt FW. Chromosomal Loop Domains Direct the Recombination of Antigen Receptor Genes. Cell 2015, 163: 947-959. PMID: 26593423, PMCID: PMC4660266, DOI: 10.1016/j.cell.2015.10.016.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCCCTC-Binding FactorChromosomes, MammalianDNA-Binding ProteinsGenes, mycGenomeHigh-Throughput Nucleotide SequencingHomeodomain ProteinsHumansImmunoglobulin Heavy ChainsLymphomaMiceNucleotide MotifsRegulatory Sequences, Nucleic AcidRepressor ProteinsSequence Analysis, DNATranslocation, GeneticV(D)J RecombinationConceptsRecombination signal sequencesRSS pairAntigen receptor genesSignal sequenceRAG activityDNA breaksChromosomal loopsLoop domainBiological processesConvergent CTCFChromosomal translocationsCleavage siteReceptor geneTarget activitySuch breaksMarked orientation dependenceRecombinationRAGCTCFChromatinMegabasesOff-target distributionGenesBreaksDomainGenomic landscape of cutaneous T cell lymphoma
Choi J, Goh G, Walradt T, Hong BS, Bunick CG, Chen K, Bjornson RD, Maman Y, Wang T, Tordoff J, Carlson K, Overton JD, Liu KJ, Lewis JM, Devine L, Barbarotta L, Foss FM, Subtil A, Vonderheid EC, Edelson RL, Schatz DG, Boggon TJ, Girardi M, Lifton RP. Genomic landscape of cutaneous T cell lymphoma. Nature Genetics 2015, 47: 1011-1019. PMID: 26192916, PMCID: PMC4552614, DOI: 10.1038/ng.3356.Peer-Reviewed Original Research
2014
The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells
Karo JM, Schatz DG, Sun JC. The RAG Recombinase Dictates Functional Heterogeneity and Cellular Fitness in Natural Killer Cells. Cell 2014, 159: 94-107. PMID: 25259923, PMCID: PMC4371485, DOI: 10.1016/j.cell.2014.08.026.Peer-Reviewed Original ResearchConceptsRecombination-activating geneDNA damage response mediatorsInnate lymphoid cellsNatural killer cellsAntigen receptor genesCellular fitnessJawed vertebratesRAG recombinaseCellular stressInnate lymphocytesNovel functionDNA breaksKiller cellsEndonuclease activityUnexpected roleCleavage eventsAdaptive immune cellsReceptor geneReduced expressionGenesFunctional heterogeneityCellsImmune cellsResponse mediatorsFitness
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 stimulationMultiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes
Duke JL, Liu M, Yaari G, Khalil AM, Tomayko MM, Shlomchik MJ, Schatz DG, Kleinstein SH. Multiple Transcription Factor Binding Sites Predict AID Targeting in Non-Ig Genes. The Journal Of Immunology 2013, 190: 3878-3888. PMID: 23514741, PMCID: PMC3689293, DOI: 10.4049/jimmunol.1202547.Peer-Reviewed Original ResearchConceptsTranscription Factor Binding SitesAID-induced lesionsNon-Ig genesGenome instabilityTranscription factorsAberrant targetingSequence dataCertain genesGenesAID targetingGerminal center B cellsSomatic mutationsLikely targetBinding sitesAID targetsTargetingClassification tree modelMistargetingB cellsLociMechanismTargetMutationsSites
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
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
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
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
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
Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates*
Yang SY, Fugmann SD, Gramlich HS, Schatz DG. Activation-induced Cytidine Deaminase-mediated Sequence Diversification Is Transiently Targeted to Newly Integrated DNA Substrates*. Journal Of Biological Chemistry 2007, 282: 25308-25313. PMID: 17613522, DOI: 10.1074/jbc.m704231200.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseChicken B cell line DT40B cell line DT40Cytidine deaminaseNon-Ig lociNon-Ig genesSequence diversificationDNA substratesTranscription cassetteMutation targetsCassetteMolecular characteristicsMolecular featuresDeaminaseDT40TranscriptionGenesLociDNADiversificationMutabilityTargetingIgTargetTargeting 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
2005
Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System
Shockett P, Schatz D. Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System. Current Protocols In Cell Biology 2005, 27: 20.8.1-20.8.10. PMID: 18228465, DOI: 10.1002/0471143030.cb2008s27.Peer-Reviewed Original ResearchConceptsInducible gene expressionSelectable markerGene expressionSecond selectable markerCell linesFibroblast cell lineTransient transfectionGene protein expressionResultant clonesStable linesMarker plasmidPlasmidProtein expressionAdherent cellsTransactivatorExpressionTransfectionCellsTargetGenesSupport protocolClonesLinesMarkersAutoregulatoryBiochemistry 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
Antigen receptor genes and the evolution of a recombinase
Schatz DG. Antigen receptor genes and the evolution of a recombinase. Seminars In Immunology 2004, 16: 245-256. PMID: 15522623, DOI: 10.1016/j.smim.2004.08.004.Peer-Reviewed Original ResearchConceptsAntigen receptor genesReceptor geneDNA repair factorsSite-specific recombination reactionRAG transposonVertebrate genomesJawed vertebratesEvolutionary implicationsRAG2 proteinsTransposable elementsRepair factorsGenesAdaptive immune systemHorizontal transmissionRAG1VertebratesGenomeImmune systemTransposonGermlineRecombinaseRAG2ProteinRecombination reactionRecombinationCloning of Apoptosis-Related Genes by Representational Difference Analysis of cDNA
Hubank M, Bryntesson F, Regan J, Schatz DG. Cloning of Apoptosis-Related Genes by Representational Difference Analysis of cDNA. Methods In Molecular Biology 2004, 282: 255-273. PMID: 15105570, DOI: 10.1385/1-59259-812-9:255.Peer-Reviewed Original ResearchConceptsRepresentational difference analysisApoptosis-related genesComplementary DNA representational difference analysisCDNA-RDAGene expressionDifferential gene expression analysisIdentification of genesKey target genesExpression levelsGene expression analysisLow-abundance transcriptsGene microarray analysisModel organismsTranscriptional differencesTarget genesExpression analysisDifferential displayMicroarray analysisGene microarrayCDNA fragmentsCDNA ampliconsGenesBase pairsSerial analysisPolymerase chain reaction amplification
2002
Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System
Shockett P, Schatz D. Inducible Gene Expression Using an Autoregulatory, Tetracycline‐Controlled System. Current Protocols In Molecular Biology 2002, 60: 16.14.1-16.14.9. PMID: 18265300, DOI: 10.1002/0471142727.mb1614s60.Peer-Reviewed Original ResearchConceptsInducible gene expressionSelectable markerGene expressionSecond selectable markerCell linesFibroblast cell lineTransient transfectionGene protein expressionResultant clonesStable linesMarker plasmidPlasmidProtein expressionAdherent cellsTransactivatorExpressionTransfectionCellsTargetGenesSupport protocolClonesLinesMarkersAutoregulatoryThe 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