2026-06-14T03:54:01Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/262152025-12-18T12:57:05Zcom_20.500.12105_2327com_20.500.12105_2290col_20.500.12105_16991

00925njm 22002777a 4500 dc Toiber, Debra author Erdel, Fabian author Bouazoune, Karim author Silberman, Dafne M author Zhong, Lei author Mulligan, Peter author Sebastian, Carlos author Cosentino, Claudia author Martinez-Pastor, Barbara author Giacosa, Sofia author D'Urso, Agustina author Näär, Anders M author Kingston, Robert author Rippe, Karsten author Mostoslavsky, Raul author 2013-08-22 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. Mol Cell . 2013 Aug 22;51(4):454-68. Mol Cell 23911928 https://hdl.handle.net/20.500.12105/26215 HISTONE DEACETYLASE SIRT6 DOUBLE-STRAND BREAKS HOMOLOGOUS RECOMBINATION DAMAGE RESPONSEFACTOR CHD4 HUMAN-CELLS REPAIR ACETYLATION RESECTIONH3 SIRT6 recruits SNF2H to DNA break sites, preventing genomic instability through chromatin remodeling.