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Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex

Opened Access Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex

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Autor: Gómez González, Belén
Aguilera López, Andrés
Departamento: Universidad de Sevilla. Departamento de Genética
Fecha: 2007
Publicado en: Proceedings of the National Academy of Sciences of the United States of America, 104(20), 8409–8414
Tipo de documento: Artículo
Resumen: 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 divers...
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Cita: Gómez González, B. y Aguilera López, A. (2007). Activation-induced cytidine deaminase action is strongly stimulated by mutations of the THO complex. Proceedings of the National Academy of Sciences of the United States of America, 104 (20), 8409-8414.
Tamaño: 917.0Kb
Formato: PDF

URI: http://hdl.handle.net/11441/29086

DOI: http://dx.doi.org/10.1073/pnas.0702836104

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