%0 Journal Article
%T Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes
%A Vladimir I Mayorov
%A Igor B Rogozin
%A Linda R Adkison
%A Christin Frahm
%A Thomas A Kunkel
%A Youri I Pavlov
%J BMC Immunology
%D 2005
%I BioMed Central
%R 10.1186/1471-2172-6-10
%X To investigate the mechanisms of AID-induced mutagenesis in a model system, we studied the genetic consequences of AID expression in yeast. We constructed a yeast vector with an artificially synthesized human AID gene insert using codons common to highly expressed yeast genes. We found that expression of the artificial hAIDSc gene was moderately mutagenic in a wild-type strain and highly mutagenic in an ung1 uracil-DNA glycosylase-deficient strain. A majority of mutations were at G-C pairs. In the ung1 strain, C-G to T-A transitions were found almost exclusively, while a mixture of transitions with 12% transversions was characteristic in the wild-type strain. In the ung1 strain mutations that could have originated from deamination of the transcribed stand were found more frequently. In the wild-type strain, the strand bias was reversed. DGYW/WRCH motifs were preferential sites of mutations.The results are consistent with the hypothesis that AID-mediated deamination of DNA is a major cause of mutations at G-C base pairs in immunoglobulin genes during SHM. The sequence contexts of mutations in yeast induced by AID and those of somatic mutations at G-C pairs in immunoglobulin genes are significantly similar. This indicates that the intrinsic substrate specificity of AID itself is a primary determinant of mutational hotspots at G-C base pairs during SHM.The immune system uses several strategies to modify genetic material to generate various types of high affinity antibodies [1]. These strategies enable production of multiple antibody variants to a wide range of different antigens [2]. Initially, antigen receptors are generated by a site-specific recombination process called V(D)J recombination occurring in the bone marrow [3]. However, this is not sufficient to assure an adequate immune response. Mature B-lymphocytes migrate to the secondary lymphoid organs where they encounter antigens. Upon activation by antigens, mature B-lymphocytes begin to proliferate and form ger
%U http://www.biomedcentral.com/1471-2172/6/10