title: Artemis, a novel DNA double-strand break repair/V(D)J recombination protein, is mutated in human severe combined immune deficiency.
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.
authors.affiliation: Développement Normal et Pathologique, du Système Immunitaire, INSERM U429, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015, Paris, France.
authors.forename: D
authors.initials: D
authors.lastname: Moshous
authors.forename: I
authors.initials: I
authors.lastname: Callebaut
authors.forename: R
authors.initials: R
authors.lastname: de Chasseval
authors.forename: B
authors.initials: B
authors.lastname: Corneo
authors.forename: M
authors.initials: M
authors.lastname: Cavazzana-Calvo
authors.forename: F
authors.initials: F
authors.lastname: Le Deist
authors.forename: I
authors.initials: I
authors.lastname: Tezcan
authors.forename: O
authors.initials: O
authors.lastname: Sanal
authors.forename: Y
authors.initials: Y
authors.lastname: Bertrand
authors.forename: N
authors.initials: N
authors.lastname: Philippe
authors.forename: A
authors.initials: A
authors.lastname: Fischer
authors.forename: J P
authors.initials: JP
authors.lastname: de Villartay
mesh_terms: D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000502:physiology*; D001483:Base Sequence; D015152:Blotting, Northern; D002478:Cells, Cultured; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D003001:Cloning, Molecular; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005347:Fibroblasts; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D017434:Protein Structure, Tertiary; D011836:Radiation Tolerance / Q000235:genetics*; D011995:Recombination, Genetic / Q000235:genetics*; D016415:Sequence Alignment; D016511:Severe Combined Immunodeficiency / Q000235:genetics* / Q000503:physiopathology; D013601:T-Lymphocytes / Q000502:physiology*; D014162:Transfection; D001618:beta-Lactamases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C426344:DCLRE1C protein, human; D004720:Endonucleases; D001618:beta-Lactamases