| Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G. | |
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MedLine Citation:
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PMID: 19022738 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced (cytidine) deaminase (AID) efficiently introduces multiple and diversified deaminations in immunoglobulin (Ig) variable and switch regions. Here, we review studies of AID, and the APOBEC family member, APOBEC3G, demonstrating that both enzymes introduce multiple deaminations by processive action on single-stranded DNA and that deaminations occur stochastically at hot- and cold-spot targets. In a more detailed analysis of AID, we examine phosphorylation-null mutants, particularly, S38A and S43P. S43P mutant AID has been identified in a patient with hyper-IgM immunodeficiency syndrome. The phosphorylation-null mutants have essentially the same specific activity, processivity and ability to undergo transcription-dependent deamination compared with wild-type (WT) AID. Although the phosphorylation-null mutants still deaminate 5'-WRC hot spots, the mutant deamination spectra differ from WT AID. The mutants strongly prefer two motifs, 5'AGC and 5'GGC, which are disfavoured by WT AID. Differences in deamination specificities can be attributed primarily to the replacement of Ser rather than to the absence of phosphorylation. The 5'GGC motif occurs with exceptionally high frequency on the non-transcribed strand of human switch regions, IgG4 and IgE. The potential for S43P to catalyse large numbers of aberrant deaminations in switch region sequences suggests a possible relationship between non-canonical AID deamination specificity and a loss of antibody diversification. |
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Authors:
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Linda Chelico; Phuong Pham; Myron F Goodman |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: Philosophical transactions of the Royal Society of London. Series B, Biological sciences Volume: 364 ISSN: 1471-2970 ISO Abbreviation: Philos. Trans. R. Soc. Lond., B, Biol. Sci. Publication Date: 2009 Mar |
Date Detail:
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Created Date: 2009-01-29 Completed Date: 2009-03-27 Revised Date: 2010-09-23 |
Medline Journal Info:
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Nlm Unique ID: 7503623 Medline TA: Philos Trans R Soc Lond B Biol Sci Country: England |
Other Details:
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Languages: eng Pagination: 583-93 Citation Subset: IM |
Affiliation:
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Department of Biological Sciences, University of Southern California, Los Angeles, CA 90089-2910, USA. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Antibodies
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genetics Cytidine Deaminase / metabolism* Deamination Humans Hyper-IgM Immunodeficiency Syndrome / genetics* Immunoglobulin Class Switching / immunology* Models, Genetic Mutation / genetics Phosphorylation Stochastic Processes* |
| Grant Support | |
ID/Acronym/Agency:
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ESO13192//PHS HHS; R37GM21422/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/APOBEC3G protein, human; EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
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