Artículo
Partial depletion of histone H4 increases homologous recombination-mediated genetic instability
Autor/es | Prado Velasco, José Félix
Aguilera López, Andrés |
Departamento | Universidad de Sevilla. Departamento de Genética |
Fecha de publicación | 2005 |
Fecha de depósito | 2017-07-05 |
Publicado en |
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Resumen | DNA replication can be a source of genetic instability. Given the tight connection between DNA replication
and nucleosome assembly, we analyzed the effect of a partial depletion of histone H4 on genetic instability
mediated ... DNA replication can be a source of genetic instability. Given the tight connection between DNA replication and nucleosome assembly, we analyzed the effect of a partial depletion of histone H4 on genetic instability mediated by homologous recombination. A Saccharomyces cerevisiae strain was constructed in which the expression of histone H4 was driven by the regulated tet promoter. In agreement with defective nucleosome assembly, partial depletion of histone H4 led to subtle changes in plasmid superhelical density and chromatin sensitivity to micrococcal nuclease. Under these conditions, homologous recombination between ectopic DNA sequences was increased 20-fold above the wild-type levels. This hyperrecombination was not associated with either defective repair or transcription but with an accumulation of recombinogenic DNA lesions during the S and G2/M phases, as determined by an increase in the proportion of budded cells containing Rad52-yellow fluorescent protein foci. Consistently, partial depletion of histone H4 caused a delay during the S and G2/M phases. Our results suggest that histone deposition defects lead to the formation of recombinogenic DNA structures during replication that increase genomic instability. |
Agencias financiadoras | Ministerio de Ciencia y Tecnología (MCYT). España |
Identificador del proyecto | BMC2000-0439
SAF2003-00204 |
Cita | Prado Velasco, J.F. y Aguilera López, A. (2005). Partial depletion of histone H4 increases homologous recombination-mediated genetic instability. Molecular and Cellular Biology, 25 (4), 1526-1536. |
Ficheros | Tamaño | Formato | Ver | Descripción |
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Partial Depletion of Histone.pdf | 613.0Kb | [PDF] | Ver/ | |