2018
DNA melting initiates the RAG catalytic pathway
Ru H, Mi W, Zhang P, Alt FW, Schatz DG, Liao M, Wu H. DNA melting initiates the RAG catalytic pathway. Nature Structural & Molecular Biology 2018, 25: 732-742. PMID: 30061602, PMCID: PMC6080600, DOI: 10.1038/s41594-018-0098-5.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesDNA meltingCryo-EM structureBase-specific contactsSignal sequenceDNA transpositionSubstrate bindingRetroviral integrationRAG endonucleaseDimer openingTerminal sequenceGTG sequenceDNA cleavageScissile phosphateDNAUniversal mechanismPiston-like movementSequenceActive siteHeptamerRetrotransposonsCatalytic pathwayTransposonComplexesEndonuclease
2015
RAG Represents a Widespread Threat to the Lymphocyte Genome
Teng G, Maman Y, Resch W, Kim M, Yamane A, Qian J, Kieffer-Kwon KR, Mandal M, Ji Y, Meffre E, Clark MR, Cowell LG, Casellas R, Schatz DG. RAG Represents a Widespread Threat to the Lymphocyte Genome. Cell 2015, 162: 751-765. PMID: 26234156, PMCID: PMC4537821, DOI: 10.1016/j.cell.2015.07.009.Peer-Reviewed Original ResearchConceptsRecombination signalsStrong recombination signalGenome stabilityHuman genomeActive promotersGenomeDNA damageChromosomal translocationsCleavage siteWidespread threatRAG1Lymphocyte genomeEvolutionary struggleRecombinationRAGChromatinPromoterEndonucleaseSitesRAG2TranslocationAbundanceDepletionEnhancerHeptamer
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
2003
A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences
Lee AI, Fugmann SD, Cowell LG, Ptaszek LM, Kelsoe G, Schatz DG. A Functional Analysis of the Spacer of V(D)J Recombination Signal Sequences. PLOS Biology 2003, 1: e1. PMID: 14551903, PMCID: PMC212687, DOI: 10.1371/journal.pbio.0000001.Peer-Reviewed Original ResearchConceptsRecombination signal sequencesSignal sequenceGene segmentsProtein-DNA interactionsLevel of recombinationDegree of conservationParticular functional importanceJ gene segmentsAntigen receptor genesSpacer variantsRAG proteinsRecombination machineryRSS activityInactive pseudogeneRSS functionSpacer sequencesFunctional analysisInteraction surfaceFunctional importanceLymphocyte developmentNumerous complex interactionsBiochemical assaysDistinct cooperationReceptor geneHeptamer
1996
RAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination
Difilippantonio M, McMahan C, Eastman Q, Spanopoulou E, Schatz D. RAG1 Mediates Signal Sequence Recognition and Recruitment of RAG2 in V(D)J Recombination. Cell 1996, 87: 253-262. PMID: 8861909, DOI: 10.1016/s0092-8674(00)81343-4.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell LineDNA NucleotidyltransferasesDNA-Binding ProteinsGenes, ImmunoglobulinHomeodomain ProteinsHumansMacromolecular SubstancesMolecular Sequence DataNuclear ProteinsProtein BindingProteinsRecombinant ProteinsRecombination, GeneticSalmonellaSequence AlignmentStructure-Activity RelationshipTranscriptional ActivationTransfectionConceptsDNA bindingAbsence of RAG2Signal sequence recognitionRegion of RAG1RAG2 proteinsBacterial invertasesSequence similarityRecombination signalsSpecific binding interactionsRAG1Sequence recognitionDNA cleavageRAG2Binding interactionsProteinBindingRecombinationRecent studiesSignal recognitionInvertaseHeptamerRecruitmentCleavageLocalizationVivoInitiation 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