{"doi":"10.17615/xtpr-cx36","title":"VprBP binds full-length RAG1 and is required for B-cell development and V(D)J recombination fidelity","abstract":"The N-terminus of full-length RAG1, though dispensable for RAG1/2 cleavage activity, is required for efficient V(D)J recombination. This region supports RING E3 ubiquitin ligase activity in vitro, but whether full-length RAG1 functions as a single subunit or a multi-subunit E3 ligase in vivo is unclear. We show the multi-subunit cullin RING E3 ligase complex VprBP/DDB1/Cul4A/Roc1 associates with full-length RAG1 through VprBP. This complex is assembled into RAG protein–DNA complexes, and supports in-vitro ubiquitylation activity that is insensitive to RAG1 RING domain mutations. Conditional B lineage-specific VprBP disruption arrests B-cell development at the pro-B-to-pre-B cell transition, but this block is bypassed by expressing rearranged immunoglobulin transgenes. Mice with a conditional VprBP disruption show modest reduction of D–JH rearrangement, whereas VH–DJH and Vκ–Jκ rearrangements are severely impaired. D–JH coding joints from VprBP-insufficent mice show longer junctional nucleotide insertions and a higher mutation frequency in D and J segments than normal. These data suggest full-length RAG1 recruits a cullin RING E3 ligase complex to ubiquitylate an unknown protein(s) to limit error-prone repair during V(D)J recombination.","journal":"UNC Libraries","year":2020,"id":137489,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9554,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":598117,"name":"Michele D. Kassmeier","orcid":null,"position":1,"is_corresponding":false},{"id":598118,"name":"Prafulla Raval","orcid":null,"position":2,"is_corresponding":false},{"id":284197,"name":"Sarah E. Jackson","orcid":"0000-0001-5658-6168","position":3,"is_corresponding":false},{"id":390733,"name":"Paweł Ciborowski","orcid":"0000-0001-6912-101X","position":4,"is_corresponding":false},{"id":597474,"name":"Victoria Palmer","orcid":"0000-0003-0507-8862","position":5,"is_corresponding":false},{"id":597475,"name":"Patrick C. Swanson","orcid":"0000-0002-3290-6582","position":6,"is_corresponding":false},{"id":275964,"name":"Koushik Mondal","orcid":"0000-0001-6557-4273","position":7,"is_corresponding":false},{"id":598119,"name":"Dirk K. Anderson","orcid":null,"position":8,"is_corresponding":false},{"id":597476,"name":"Greg A. Perry","orcid":"0000-0003-1162-0080","position":9,"is_corresponding":false},{"id":63630,"name":"Yue Xiong","orcid":"0000-0003-2744-6566","position":10,"is_corresponding":false},{"id":597473,"name":"Sushil Kumar","orcid":"0000-0003-1837-7191","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:56.001887Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}