title: The cytidine deaminase AID exhibits similar functional properties in yeast and mammals.
abstract: A recent work published in Molecular Immunology examined the editing activity of activation-induced deaminase (AID) in yeast (Krause, K., Marcu, K.B., Greeve, J., 2006. The cytidine deaminases AID and APOBEC-1 exhibit distinct functional properties in a novel yeast selectable system. Mol. Immunol.). It was proposed that expression of AID in yeast is not sufficient for the generation of point mutations in a highly transcribed gene due to the lack of cofactors for AID-induced somatic hypermutation, which are unique to B cells. It was suggested that, on its own, AID does not have an intrinsic specificity for its target sequences. However, it has been shown previously that expression of the human AID gene in yeast was moderately mutagenic in a wild-type strain and highly mutagenic in an ung1 uracil-DNA glycosylase-deficient strain (Mayorov, V.I., Rogozin, I.B., Adkison, L.R., Frahm, C.R., Kunkel T.A., Pavlov Y. I., 2005. Expression of human AID in yeast induces mutations in context similar to the context of somatic hypermutation at G-C pairs in immunoglobulin genes. BMC Immunol. 6, 10; Poltoratsky, V.P., Wilson, S.H., Kunkel, T.A., Pavlov, Y.I., 2004. Recombinogenic phenotype of human activation-induced cytosine deaminase. J. Immunol. 172, 4308-4313). The vast majority of mutations were at G-C pairs. Mutations showed a clear DNA sequence context specificity which resembled the specificity of somatic hypermutation at G-C pairs in immunoglobulin genes and AID mutation specificity in vitro. The inability to detect mutator effects of AID by Krause et al. is likely to be caused by the use of the wild-type yeast strain and a small sample of clones examined for the presence of mutations. In addition, we show that non-uniformity of the mutation hotspot distribution is a factor potentially decreasing the chances of detecting mutations.
authors.affiliation: National Center for Biotechnology Information NLM, National Institutes of Health, 8600 Rockville Pike, Bldg. 38A/room 5N505A, Bethesda, MD 20894, USA. rogozin@ncbi.nlm.nih.gov
authors.forename: Igor B
authors.initials: IB
authors.lastname: Rogozin
authors.forename: Youri I
authors.initials: YI
authors.lastname: Pavlov
mesh_terms: D000818:Animals; D003564:Cytidine Deaminase / Q000235:genetics / Q000378:metabolism*; D043525:Cytosine Deaminase / Q000235:genetics / Q000378:metabolism*; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D005800:Genes, Fungal; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics; D027041:Somatic Hypermutation, Immunoglobulin; D013045:Species Specificity; D000098830:AICDA (Activation-Induced Cytidine Deaminase)
chemical_list: D004271:DNA, Fungal; D011994:Recombinant Proteins; D000098830:AICDA (Activation-Induced Cytidine Deaminase); D043525:Cytosine Deaminase; D003564:Cytidine Deaminase