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Uracil residues dependent on the deaminase AID in immunoglobulin gene variable and switch regions.
- Source :
-
Nature immunology [Nat Immunol] 2011 Jan; Vol. 12 (1), pp. 70-6. Date of Electronic Publication: 2010 Dec 12. - Publication Year :
- 2011
-
Abstract
- Activation-induced deaminase (AID) initiates diversity of immunoglobulin genes through deamination of cytosine to uracil. Two opposing models have been proposed for the deamination of DNA or RNA by AID. Although most data support DNA deamination, there is no physical evidence of uracil residues in immunoglobulin genes. Here we demonstrate their presence by determining the sensitivity of DNA to digestion with uracil DNA glycosylase (UNG) and abasic endonuclease. Using several methods of detection, we identified uracil residues in the variable and switch regions. Uracil residues were generated within 24 h of B cell stimulation, were present on both DNA strands and were found to replace mainly cytosine bases. Our data provide direct evidence for the model that AID functions by deaminating cytosine residues in DNA.
- Subjects :
- Animals
Antigenic Variation genetics
B-Lymphocytes immunology
B-Lymphocytes pathology
Cells, Cultured
Cytidine Deaminase genetics
DNA-(Apurinic or Apyrimidinic Site) Lyase genetics
Immunoglobulin Class Switching
Immunoglobulin Variable Region
Interleukin-4 immunology
Interleukin-4 metabolism
Lipopolysaccharides immunology
Lipopolysaccharides metabolism
Lymphocyte Activation genetics
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Chemical
Spleen pathology
Uracil analysis
Uracil-DNA Glycosidase genetics
B-Lymphocytes metabolism
Cytidine Deaminase metabolism
DNA-(Apurinic or Apyrimidinic Site) Lyase metabolism
Uracil-DNA Glycosidase metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1529-2916
- Volume :
- 12
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Nature immunology
- Publication Type :
- Academic Journal
- Accession number :
- 21151102
- Full Text :
- https://doi.org/10.1038/ni.1970