Artículo
SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling
Toiber, Deborah; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne Magali
; Zhong, Lei; Mulligan, Peter; Sebastián, Carlos; Cosentino, Claudia; Martínez Pastor, Bárbara; Giacosa, Sofia; D´Urso, Agustina; Näär, Anders M.; Kingston, Robert; Rippe, Karsten; Mostoslavsky, Raul
Fecha de publicación:
08/2013
Editorial:
Cell Press
Revista:
Molecular Cell
ISSN:
1097-2765
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
DNA damage is linked to multiple human diseases, such as cancer, neurodegeneration, and aging. Little is known about the role of chromatin accessibility in DNA repair. Here, we find that the deacetylase sirtuin 6 (SIRT6) is one of the earliest factors recruited to double-strand breaks (DSBs). SIRT6 recruits the chromatin remodeler SNF2H to DSBs and focally deacetylates histone H3K56. Lack of SIRT6 and SNF2H impairs chromatin remodeling, increasing sensitivity to genotoxic damage and recruitment of downstream factors such as 53BP1 and breast cancer 1 (BRCA1). Remarkably, SIRT6-deficient mice exhibit lower levels of chromatin-associated SNF2H in specific tissues, a phenotype accompanied by DNA damage. We demonstrate that SIRT6 is critical for recruitment of a chromatin remodeler as an early step in the DNA damage response, indicating that proper unfolding of chromatin plays a rate-limiting role. We present a unique crosstalk between a histone modifier and a chromatin remodeler, regulating a coordinated response to prevent DNA damage.
Palabras clave:
Sirt6
,
Cromatina
,
Epigenetica
Archivos asociados
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Identificadores
Colecciones
Articulos(CEFYBO)
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Articulos de CENTRO DE ESTUDIOS FARMACOLOGICOS Y BOTANICOS
Citación
Toiber, Deborah; Erdel, Fabian; Bouazoune, Karim; Silberman, Dafne Magali; Zhong, Lei; et al.; SIRT6 recruits SNF2H to sites of DNA breaks, preventing genomic instability through chromatin remodeling; Cell Press; Molecular Cell; 51; 4; 8-2013; 454-468
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