Artemis sheds new light on V(D)J recombination.
V(D)J recombination represents one of the three mechanisms that contribute to the diversity of the immune repertoire of B lymphocytes and T lymphocytes. It also constitutes a major checkpoint during the development of the immune system. Indeed, any V(D)J recombination deficiency leads to a block of B-cell and T-cell maturation in humans and animal models, leading to severe combined immunodeficiency (T-B-SCID). Nine factors have been identified so far to participate in V(D)J recombination. The discovery of Artemis, mutated in a subset of T-B-SCID, provided some new information regarding one of the missing V(D)J recombinase activities: hairpin opening at coding ends prior to DNA repair of the recombination activating genes 1/2-generated DNA double-strand break. New conditions of immune deficiency in humans are now under investigations and should lead to the identification of additional V(D)J recombination/DNA repair factors.
Le Deist
Françoise
F
Développement Normal et Pathologique du Système Immunitaire, INSERM U429, Paris, France.
Poinsignon
Catherine
C
Moshous
Despina
D
Fischer
Alain
A
de Villartay
Jean-Pierre
JP
D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases; D015322:Gene Rearrangement, B-Lymphocyte / Q000502:physiology*; D015329:Gene Rearrangement, T-Lymphocyte / Q000502:physiology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007154:Immune System Diseases / Q000201:enzymology; D009687:Nuclear Proteins / Q000276:immunology / Q000502:physiology*; D011995:Recombination, Genetic; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D001618:beta-Lactamases / Q000276:immunology / Q000502:physiology
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D009687:Nuclear Proteins; C499311:RAG2 protein, human; C064655:V(D)J recombination activating protein 2; C064658:RAG-1 protein; C426344:DCLRE1C protein, human; D004720:Endonucleases; D001618:beta-Lactamases