D. Moshous et al., Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency, CELL, 105(2), 2001, pp. 177-186
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.