The contested role of uracil DNA glycosylase in immunoglobulin gene diversification.
Class switch recombination (CSR) and somatic hypermutation (SHM) of immunoglobulin (Ig) genes are initiated by the activation-induced cytosine deaminase AID. The resulting uracils in Ig genes were believed to be removed by the uracil glycosylase (UNG) and the resulting abasic sites treated in an error-prone fashion, creating breaks in the Ig switch regions and mutations in the variable regions. A recent report suggests that UNG does not act as a glycosylase in CSR and SHM but rather has unknown activity subsequent to DNA breaks that were created by other mechanisms.
Longerich
Simonne
S
Department of Molecular Genetics and Cell Biology, Committee on Immunology, University of Chicago, IL 60637, USA.
Storb
Ursula
U
D000818:Animals; D003564:Cytidine Deaminase / Q000502:physiology*; D045647:DNA Glycosylases / Q000502:physiology*; D005803:Genes, Immunoglobulin; D006801:Humans; D007105:Immune Complex Diseases / Q000235:genetics* / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology; D011995:Recombination, Genetic; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics* / Q000276:immunology; D051981:Uracil-DNA Glycosidase; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
D045647:DNA Glycosylases; D051981:Uracil-DNA Glycosidase; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D003564:Cytidine Deaminase