title: Inherited defects of immunoglobulin class switch recombination.
abstract: The investigation of an inherited primary immunodeficiency, the immunoglobulin class switch recombination deficiency, has allowed the delineation of complex molecular events that underlie antibody maturation in humans. The Activation-induced cytidine deaminase (AID)-deficiency, characterized by a defect in Class Switch Recombination (CSR) and somatic hypermutation, has revealed the master role of this molecule in the induction of DNA damage, the first step required for these two processes. The description that mutations in the gene encoding the Uracil-DNA glycosylase (UNG) lead to defective CSR has been essential for defining the DNA-editing activity of AID. Analysis of post meiotic segregation 2 (PMS2)-deficient patients gave evidence for the role of this mismatch repair enzyme in the generation of the DNA breaks that are required for CSR. Novel findings are awaited from the study ofyet-genetically undefined CSR-deficiencies, probably leading to the identification of AID cofactor(s) and/or proteins involved in CSR-induced DNA repair.
authors.affiliation: INSERM, U768; Université Paris Descartes, Faculté de Médecine René Descartes, Paris, F-75005, France.
authors.forename: Sven
authors.initials: S
authors.lastname: Kracker
authors.forename: Pauline
authors.initials: P
authors.lastname: Gardës
authors.forename: Anne
authors.initials: A
authors.lastname: Durandy
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism; D053960:DNA Breaks; D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D049914:DNA Repair-Deficiency Disorders / Q000201:enzymology / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D030342:Genetic Diseases, Inborn / Q000201:enzymology / Q000235:genetics; D006801:Humans; D017578:Immunoglobulin Class Switching; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics; D000070976:Mismatch Repair Endonuclease PMS2; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin; D051981:Uracil-DNA Glycosidase / Q000235:genetics / Q000378:metabolism; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004268:DNA-Binding Proteins; D051981:Uracil-DNA Glycosidase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase; D000251:Adenosine Triphosphatases; C094934:PMS2 protein, human; D000070976:Mismatch Repair Endonuclease PMS2; D045643:DNA Repair Enzymes