Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency

The V(D)J recombination process insures the somatic diversification of immu noglobulin and antigen T cell receptor encoding genes. This reaction is ini tiated by a DNA double-strand break (dsb), which is resolved by the ubiquit ously expressed DNA repair machinery. Human T-B-severe combined immunodefic iency associated with increased cellular radiosensitivity (RS-SCID) is char acterized by a defect in the V(D)J recombination leading to an early arrest of both B and T cell maturation. We previously mapped the disease-related locus to the short arm of chromosome 10. We herein describe the cloning of the gene encoding a novel protein involved in V(D)J recombination/DNA repai r, Artemis, whose mutations cause human RS-SCID. Protein sequence analysis strongly suggests that Artemis belongs to the metallo-beta -lactamase super family.