Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency
D Moshous, I Callebaut, R de Chasseval, B Corneo, M Cavazzana-Calvo, F Le Deist, I Tezcan, O Sanal, Y Bertrand, N Philippe, A Fischer, J P de Villartay, D Moshous, I Callebaut, R de Chasseval, B Corneo, M Cavazzana-Calvo, F Le Deist, I Tezcan, O Sanal, Y Bertrand, N Philippe, A Fischer, J P de Villartay
Abstract
The V(D)J recombination process insures the somatic diversification of immunoglobulin and antigen T cell receptor encoding genes. This reaction is initiated by a DNA double-strand break (dsb), which is resolved by the ubiquitously expressed DNA repair machinery. Human T-B-severe combined immunodeficiency associated with increased cellular radiosensitivity (RS-SCID) is characterized 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 repair, Artemis, whose mutations cause human RS-SCID. Protein sequence analysis strongly suggests that Artemis belongs to the metallo-beta-lactamase superfamily.
Source: PubMed