V(D)J recombination deficiencies.
V(D)J recombination not only comprises the molecular mechanism that insures diversity of the immune system but also constitutes a critical checkpoint in the developmental program of B- and T-lymphocytes. The analysis of human patients with Severe Combined Immune Deficiency (SCID) has contributed to the understanding of the biochemistry of the V(D)J recombination reaction. The molecular study V(D)J recombination settings in humans, mice and in cellular mutants has allowed to unravel the process of Non Homologous End Joining (NHEJ), one of the key pathway that insure proper repair of DNA double strand breaks (dsb), whether they occur during V(D)J recombination or secondary to other DNA injuries. Two NHEJ factors, Artemis and Cernunnos, were indeed discovered through the study of human V(D)J recombination defective human SCID patients.
de Villartay
Jean-Pierre
JP
INSERM U768, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France. devillar@necker.fr
D000818:Animals; D004249:DNA Damage; D004260:DNA Repair; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015322:Gene Rearrangement, B-Lymphocyte; D015329:Gene Rearrangement, T-Lymphocyte; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology; D013577:Syndrome; D045567:VDJ Recombinases / Q000378:metabolism
D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C508551:NHEJ1 protein, human; C499308:Rag2 protein, mouse; C064658:RAG-1 protein; D045567:VDJ Recombinases; D045643:DNA Repair Enzymes