Featured Publications
HMCES protects immunoglobulin genes specifically from deletions during somatic hypermutation
Wu L, Shukla V, Yadavalli AD, Dinesh RK, Xu D, Rao A, Schatz DG. HMCES protects immunoglobulin genes specifically from deletions during somatic hypermutation. Genes & Development 2022, 36: 433-450. PMID: 35450882, PMCID: PMC9067407, DOI: 10.1101/gad.349438.122.Peer-Reviewed Original Research
2019
Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting
Dinesh RK, Barnhill B, Ilanges A, Wu L, Michelson DA, Senigl F, Alinikula J, Shabanowitz J, Hunt DF, Schatz DG. Transcription factor binding at Ig enhancers is linked to somatic hypermutation targeting. European Journal Of Immunology 2019, 50: 380-395. PMID: 31821534, PMCID: PMC7202714, DOI: 10.1002/eji.201948357.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsChickensGenes, ImmunoglobulinHumansSomatic Hypermutation, ImmunoglobulinTranscription FactorsConceptsActivation-induced cytidine deaminaseGene conversionSomatic hypermutationIg genesTranscription factor family membersTrans-acting factorsFactor family membersClass switch recombinationEnhancer-like sequenceRamos B cell lineIgH intronic enhancerSecondary diversificationTranscription factorsE-boxFactor bindingChIP assaysIntronic enhancerReporter assaysB cell linesSpecific DNASwitch recombinationSHM targetingIg enhancersCytidine deaminaseNovel insights
2013
Multiple 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
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 locusLociAID-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
Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination
Ji Y, Little AJ, Banerjee JK, Hao B, Oltz EM, Krangel MS, Schatz DG. Promoters, enhancers, and transcription target RAG1 binding during V(D)J recombination. Journal Of Experimental Medicine 2010, 207: 2809-2816. PMID: 21115692, PMCID: PMC3005232, DOI: 10.1084/jem.20101136.Peer-Reviewed Original ResearchMeSH KeywordsAcetylationAnimalsBinding, CompetitiveChromatin ImmunoprecipitationDNAEnhancer Elements, GeneticFemaleGene RearrangementGenes, ImmunoglobulinGenotypeHistonesHMGB1 ProteinHomeodomain ProteinsMaleMiceMice, Inbred C57BLMice, KnockoutPromoter Regions, GeneticProtein BindingReceptors, Antigen, T-Cell, alpha-betaRecombination, GeneticTranscription, GeneticVDJ Recombinases
2009
Balancing AID and DNA repair during somatic hypermutation
Liu M, Schatz DG. Balancing AID and DNA repair during somatic hypermutation. Trends In Immunology 2009, 30: 173-181. PMID: 19303358, DOI: 10.1016/j.it.2009.01.007.Peer-Reviewed Original Research
2007
Role of Activation-Induced Deaminase Protein Kinase A Phosphorylation Sites in Ig Gene Conversion and Somatic Hypermutation
Chatterji M, Unniraman S, McBride KM, Schatz DG. Role of Activation-Induced Deaminase Protein Kinase A Phosphorylation Sites in Ig Gene Conversion and Somatic Hypermutation. The Journal Of Immunology 2007, 179: 5274-5280. PMID: 17911613, DOI: 10.4049/jimmunol.179.8.5274.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAmino Acid SubstitutionAnimalsAvian ProteinsCell LineChickensCyclic AMP-Dependent Protein KinasesCytidine DeaminaseEnzyme ActivationGene ConversionGenes, ImmunoglobulinHumansMiceMolecular Sequence DataPhosphorylationSerineSomatic Hypermutation, ImmunoglobulinZebrafish ProteinsConceptsReplication protein AActivation-induced deaminaseProtein kinase AClass switch recombinationGene conversionDT40 cellsPhosphorylation sitesSomatic hypermutationProtein kinase A (PKA) phosphorylation siteChicken DT40 cellsIg gene conversionEfficient gene conversionConsensus target siteIg gene diversificationGene diversificationSerine 38Cytosine residuesKinase ASwitch recombinationIg genesResidue interferesFish proteinTarget siteProtein AS38Strand-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
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
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 substratesHMG1UNGstoppable Switching
Unniraman S, Fugmann SD, Schatz DG. UNGstoppable Switching. Science 2004, 305: 1113-1114. PMID: 15326342, DOI: 10.1126/science.1102692.Peer-Reviewed Original ResearchAntigen 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 reactionRecombination
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
2002
Somatic Hypermutation of Immunoglobulin Genes Merging Mechanisms for Genetic Diversity
Papavasiliou FN, Schatz DG. Somatic Hypermutation of Immunoglobulin Genes Merging Mechanisms for Genetic Diversity. Cell 2002, 109: s35-s44. PMID: 11983151, DOI: 10.1016/s0092-8674(02)00706-7.Peer-Reviewed Original ResearchConceptsActivation-induced cytidine deaminaseSomatic hypermutationRNA editing enzymeDNA strand lesionsGenetic diversityEditing enzymeMolecular mechanismsRepair moleculesStrand lesionsCytidine deaminaseHypermutation processHypermutationRecent studiesModification reactionsEffective immune responseRecent advancesHigh-affinity antibodiesImmune responseDiversityEnzymePathwayMechanismDeaminaseDiscoveryOne AID to Unite Them All
Fugmann SD, Schatz DG. One AID to Unite Them All. Science 2002, 295: 1244-1245. PMID: 11847327, DOI: 10.1126/science.1070023.Peer-Reviewed Original Research
2001
Location, location, location: the cell biology of immunoglobulin allelic control
Hesslein D, Fields P, Schatz D. Location, location, location: the cell biology of immunoglobulin allelic control. Nature Immunology 2001, 2: 825-826. PMID: 11526394, DOI: 10.1038/ni0901-825.Peer-Reviewed Original ResearchFactors 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
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