Is Artemis the In Vivo Hairpin Opening Nuclease?
Identification and cloning of Artemis were accomplished very recently as the result of the systematic study of radiosensitive and immunodeficient (RS-SCID) patients by the de Villartay laboratory. Transformed fibroblasts from these patients were shown to have defects in VDJ recombination at the level of coding joint formation in addition to increased cellular radiosensitivity (9). The disease-related locus was mapped to chromosome 10 and subsequently cloned (10, 11). The same gene was shown to be defective in a group of Athabascan immunodeficient patients (12). Protein sequence analysis of Artemis suggested that it belongs to the metallo-ß lactamase superfamily (11). This classification was further supported by a comprehensive sequence analysis (13). Based on its exclusive effect in coding joint formation and not in signal joint formation, as well as its homology to proteins with hydrolase activity, Artemis was proposed to participate in opening the hairpin coding ends (11). This predi
