DNA repair ͉ nonhomologous end-joining ͉ V(D)J recombinationT he nonhomologous end-joining (NHEJ) pathway is conserved in eukaryotes, from yeast to humans. Without requiring homologous DNA, NHEJ repairs DNA double-strand breaks produced by xenobiotic agents, such as topoisomerase II inhibitors and ionizing radiation, or by the cellular pathway for V(D)J recombination of the immunoglobulin genes (1). Even when the structure of the DNA ends prevents ligation, NHEJ processes the ends and repairs the breaks with high efficiency and minimal nucleotide loss. For ligatable ends, such as the blunt signal ends created by V(D)J recombination, NHEJ suppresses processing and repairs the breaks directly. Thus, NHEJ optimizes the preservation of DNA sequence, but the mechanism is not understood.