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- Title
Human uracil-DNA glycosylase deficiency associated with profoundly impaired immunoglobulin class-switch recombination.
- Authors
Imai, Kohsuke; Slupphaug, Geir; Wen-I Lee; Revy, Patrick; Nonoyama, Shigeaki; Catalan, Nadia; Yel, Leman; Forveille, Monique; kavli, Bodil; Krokan, Hans E.; Ochs, Hans D.; Fischer, Alain; Durandy, Anne
- Abstract
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.
- Subjects
IMMUNOGLOBULIN M; PHENOTYPES; DNA; B cells; GENETICS
- Publication
Nature Immunology, 2003, Vol 4, Issue 10, p1023
- ISSN
1529-2908
- Publication type
Article
- DOI
10.1038/ni974