| Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex. | |
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MedLine Citation:
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PMID: 17488823 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Activation-induced cytidine deaminase (AID) is a B cell enzyme essential for Ig somatic hypermutation and class switch recombination. AID acts on ssDNA, and switch regions of Ig genes, a target of AID, form R-loops that contain ssDNA. Nevertheless, how AID action is specifically targeted to particular DNA sequences is not clear. Because mutations altering cotranscriptional messenger ribonucleoprotein (mRNP) formation such as those in THO/TREX in yeast promote R-loops, we investigated whether the cotranscriptional assembly of mRNPs could affect AID targeting. Here we show that AID action is transcription-dependent in yeast and that strong and transcription-dependent hypermutation and hyperrecombination are induced by AID if cells are deprived of THO. In these strains AID-induced mutations occurred preferentially at WRC motifs in the nontranscribed DNA strand. We propose that a suboptimal cotranscriptional mRNP assembly at particular DNA regions could play an important role in Ig diversification and genome dynamics. |
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Authors:
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Belén Gómez-González; Andrés Aguilera |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-05-08 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 104 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2007 May |
Date Detail:
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Created Date: 2007-05-22 Completed Date: 2007-07-02 Revised Date: 2009-11-18 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 8409-14 Citation Subset: IM |
Affiliation:
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Departamento de Genética, Facultad de Biología, Consejo Superior de Investigaciones Científicas-Universidad de Sevilla, Avenida Américo Vespucio s/n, 41092 Sevilla, Spain. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Cytidine Deaminase
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metabolism* Genomic Instability Models, Genetic Multiprotein Complexes / genetics* Mutation / genetics* Phenotype Recombination, Genetic / genetics Saccharomyces cerevisiae / cytology, enzymology*, genetics* Saccharomyces cerevisiae Proteins / genetics* Transcription, Genetic |
| Chemical | |
Reg. No./Substance:
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0/Multiprotein Complexes; 0/Saccharomyces cerevisiae Proteins; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
| Comments/Corrections | |
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