Intermolecular V(D)J recombination is prohibited specifically at the joining step

V(D)J recombination, normally an intramolecular process, assembles immunogl obulin and T cell receptor genes from V, D, and J coding segments. Oncogeni c chromosome translocations can result from aberrant rearrangements, such a s occur in intermolecular V(D)J recombination. How this is normally prevent ed remains unclear; DNA cleavage, joining, or both could be impaired when t he recombination signal sequences (RSS) are located in trans, on separate D NA 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 agains t intermolecular V(D)J recombination is established at the joining step, Th ese findings suggest a novel surveillance mechanism for eliminating cells c ontaining aberrant V(D)J rearrangements.