title: Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining.
abstract: DNA double-strand break (DSB) repair occurs within chromatin and can be modulated by chromatin-modifying enzymes. Here we identify the related human histone deacetylases HDAC1 and HDAC2 as two participants in the DNA-damage response. We show that acetylation of histone H3 Lys56 (H3K56) was regulated by HDAC1 and HDAC2 and that HDAC1 and HDAC2 were rapidly recruited to DNA-damage sites to promote hypoacetylation of H3K56. Furthermore, HDAC1- and 2-depleted cells were hypersensitive to DNA-damaging agents and showed sustained DNA-damage signaling, phenotypes that reflect defective DSB repair, particularly by nonhomologous end-joining (NHEJ). Collectively, these results show that HDAC1 and HDAC2 function in the DNA-damage response by promoting DSB repair and thus provide important insights into the radio-sensitizing effects of HDAC inhibitors that are being developed as cancer therapies.
authors.affiliation: The Gurdon Institute, University of Cambridge, Cambridge, UK.
authors.forename: Kyle M
authors.initials: KM
authors.lastname: Miller
authors.forename: Jorrit V
authors.initials: JV
authors.lastname: Tjeertes
authors.forename: Julia
authors.initials: J
authors.lastname: Coates
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Legube
authors.forename: Sophie E
authors.initials: SE
authors.lastname: Polo
authors.forename: Sébastien
authors.initials: S
authors.lastname: Britton
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Jackson
mesh_terms: D045744:Cell Line, Tumor; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism*; D056464:Histone Deacetylase 2 / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000378:metabolism; D006801:Humans; D034741:RNA, Small Interfering
chemical_list: D006657:Histones; D034741:RNA, Small Interfering; C110550:HDAC1 protein, human; C533423:HDAC2 protein, human; D056284:Histone Deacetylase 1; D056464:Histone Deacetylase 2
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