Intermolecular V(D)J recombination is prohibited specifically at the joining step.
V(D)J recombination, normally an intramolecular process, assembles immunoglobulin and T cell receptor genes from V, D, and J coding segments. Oncogenic chromosome translocations can result from aberrant rearrangements, such as occur in intermolecular V(D)J recombination. How this is normally prevented remains unclear; DNA cleavage, joining, or both could be impaired when the recombination signal sequences (RSS) are located in trans, on separate DNA molecules. Here, we show that both trans cleavage and joining of signal ends occur efficiently in vivo. Unexpectedly, trans joining of coding ends is severely impaired (100-to 1000-fold), indicating that protection against intermolecular V(D)J recombination is established at the joining step. These findings suggest a novel surveillance mechanism for eliminating cells containing aberrant V(D)J rearrangements.
Han
J O
JO
Department of Microbiology and Immunology, Baylor College of Medicine, Houston, Texas 77030, USA.
Steen
S B
SB
Roth
D B
DB
D000818:Animals; D001402:B-Lymphocytes; D016466:CHO Cells; D002460:Cell Line; D003062:Codon / Q000235:genetics; D006224:Cricetinae; D003434:Crossing Over, Genetic / Q000235:genetics*; D004247:DNA / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D019281:Dimerization; D005091:Exons / Q000235:genetics; D015321:Gene Rearrangement / Q000235:genetics*; D005803:Genes, Immunoglobulin / Q000235:genetics*; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics*; D051379:Mice; D010957:Plasmids / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D013997:Time Factors; D014162:Transfection
D003062:Codon; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; C499308:Rag2 protein, mouse; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; D004247:DNA