Impairment of V(D)J recombination in double-strand break repair mutants.

Cells maintain the integrity of their genome through an intricate network of repair systems that recognize and remove lesions from DNA. The only known site-directed recombination process in vertebrates is the V(D)J recombination of lymphocyte antigen receptor genes. A large panel of cell lines deficient in DNA repair were tested for the ability to perform V(D)J recombination after introduction of the RAG-1 and RAG-2 genes. Two mutants failed to generate normal V(D)J recombination, and further analysis provided evidence for two distinct nonlymphoid-specific genes that encode factors involved in both DNA repair and V(D)J recombination.