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Nat Immunol. 2003 Oct;4(10):1023-8. Epub 2003 Sep 7.

Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination.

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Institut National de la Santé et de la Recherche Médicale Unité 429, Hôpital Necker-Enfants Malades, 75015 Paris, France.


Activation-induced cytidine deaminase (AID) is a 'master molecule' in immunoglobulin (Ig) class-switch recombination (CSR) and somatic hypermutation (SHM) generation, AID deficiencies are associated with hyper-IgM phenotypes in humans and mice. We show here that recessive mutations of the gene encoding uracil-DNA glycosylase (UNG) are associated with profound impairment in CSR at a DNA precleavage step and with a partial disturbance of the SHM pattern in three patients with hyper-IgM syndrome. Together with the finding that nuclear UNG expression was induced in activated B cells, these data support a model of CSR and SHM in which AID deaminates cytosine into uracil in targeted DNA (immunoglobulin switch or variable regions), followed by uracil removal by UNG.

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