The X-ray repair cross-complementing protein XRCC4 and DNA Ligase IV are essential for repairing double-strand breaks in DNA. These proteins form a critical complex consisting of two molecules of each protein that preferentially bind DNA with nicks or broken ends. As an obligate accessory molecule, XRCC4 binds to DNA Ligase IV and enhances its joining activity. The XRCC4/ DNA Ligase IV complex is also involved in V(D)J recombination. V(D)J recombination occurs in normal development of the adaptive immune system and involves the formation of a double-strand break intermediate. Deletions of either DNA Ligase IV or XRCC4 inhibit the completion of V(D)J recombination, resulting in a high incidence of apoptosis in the developing nervous system and a block in B and T cell maturation.