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Histone methyltransferase DOT1L drives recovery of gene expression after a genotoxic attack.
Oksenych, Valentyn; Zhovmer, Alexander; Ziani, Salim; Mari, Pierre-Olivier; Eberova, Jitka; Nardo, Tiziana; Stefanini, Miria; Giglia-Mari, Giuseppina; Egly, Jean-Marc; Coin, Frédéric.
Afiliación
  • Oksenych V; IGBMC, Department of Functional Genomics and Cancer, CNRS/INSERM/Université de Strasbourg, C. U. Strasbourg, France.
PLoS Genet ; 9(7): e1003611, 2013.
Article en En | MEDLINE | ID: mdl-23861670
UV-induced DNA damage causes repression of RNA synthesis. Following the removal of DNA lesions, transcription recovery operates through a process that is not understood yet. Here we show that knocking-out of the histone methyltransferase DOT1L in mouse embryonic fibroblasts (MEF(DOT1L)) leads to a UV hypersensitivity coupled to a deficient recovery of transcription initiation after UV irradiation. However, DOT1L is not implicated in the removal of the UV-induced DNA damage by the nucleotide excision repair pathway. Using FRAP and ChIP experiments we established that DOT1L promotes the formation of the pre-initiation complex on the promoters of UV-repressed genes and the appearance of transcriptionally active chromatin marks. Treatment with Trichostatin A, relaxing chromatin, recovers both transcription initiation and UV-survival. Our data suggest that DOT1L secures an open chromatin structure in order to reactivate RNA Pol II transcription initiation after a genotoxic attack.
Asunto(s)

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Daño del ADN / Cromatina / Metiltransferasas Límite: Animals Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2013 Tipo del documento: Article País de afiliación: Francia

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Daño del ADN / Cromatina / Metiltransferasas Límite: Animals Idioma: En Revista: PLoS Genet Asunto de la revista: GENETICA Año: 2013 Tipo del documento: Article País de afiliación: Francia