2024
The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential tumorigenic activity
Šenigl F, Soikkeli A, Prost S, Schatz D, Slavková M, Hejnar J, Alinikula J. The SV40 virus enhancer functions as a somatic hypermutation-targeting element with potential tumorigenic activity. Tumour Virus Research 2024, 18: 200293. PMID: 39490533, PMCID: PMC11564006, DOI: 10.1016/j.tvr.2024.200293.Peer-Reviewed Original ResearchB cellsSV40 LTMerkel cell polyomavirusAPOBEC familySV40 enhancerCell typesAssociated with several typesAID-induced mutationsLT expressionTumorigenic potentialMalignant developmentSV40 infectionTumorigenic activityHuman cancersSomatic hypermutationAberrant expressionAntibody diversification processesSimian virusKidney cellsMonkey virusSV40Virus enhancerMutationsFrequent sourceSeveral types
2020
Disease-associated CTNNBL1 mutation impairs somatic hypermutation by decreasing nuclear AID
Kuhny M, Forbes LR, Çakan E, Vega-Loza A, Kostiuk V, Dinesh RK, Glauzy S, Stray-Pedersen A, Pezzi AE, Hanson IC, Vargas-Hernandez A, Xu ML, Akdemir Z, Jhangiani SN, Muzny DM, Gibbs RA, Lupski JR, Chinn IK, Schatz DG, Orange JS, Meffre E. Disease-associated CTNNBL1 mutation impairs somatic hypermutation by decreasing nuclear AID. Journal Of Clinical Investigation 2020, 130: 4411-4422. PMID: 32484799, PMCID: PMC7410074, DOI: 10.1172/jci131297.Peer-Reviewed Original ResearchConceptsB cellsActivation-induced cytidine deaminaseHealthy donor counterpartsIsotype-switched B cellsCommon variable immunodeficiencyMemory B cellsSomatic hypermutationAutoimmune cytopeniasDecreased incidenceVariable immunodeficiencyB cell linesUnderlying molecular defectsNuclear AIDPatient's EBVRamos B cellsPatientsProtein 1Cell linesMolecular defectsCellsCytidine deaminaseMutations
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 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
2009
Imatinib Resistance and Progression of CML to Blast Crisis: Somatic Hypermutation AIDing the Way
Strout MP, Schatz DG. Imatinib Resistance and Progression of CML to Blast Crisis: Somatic Hypermutation AIDing the Way. Cancer Cell 2009, 16: 174-176. PMID: 19732715, DOI: 10.1016/j.ccr.2009.08.012.Peer-Reviewed Original ResearchConceptsChronic myeloid leukemiaProgression of CMLColleagues present evidenceDisease progressionImatinib resistanceMyeloid leukemiaDrug resistanceCancer cellsOncogenic mutationsProgressionEnzyme activation-induced deaminaseGeneration of mutationsLeukemiaMutationsActivation-induced deaminasePresent evidence
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
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
Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage
Eastman Q, Schatz D. Nicking is asynchronous and stimulated by synapsis in 12/23 rule-regulated V(D)J cleavage. Nucleic Acids Research 1997, 25: 4370-4378. PMID: 9336470, PMCID: PMC147051, DOI: 10.1093/nar/25.21.4370.Peer-Reviewed Original Research
1996
Initiation 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