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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.

SUBMITTER: Miller KM 

PROVIDER: S-EPMC3018776 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Human HDAC1 and HDAC2 function in the DNA-damage response to promote DNA nonhomologous end-joining.

Miller Kyle M KM   Tjeertes Jorrit V JV   Coates Julia J   Legube Gaëlle G   Polo Sophie E SE   Britton Sébastien S   Jackson Stephen P SP  

Nature structural & molecular biology 20100829 9

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-damagin  ...[more]

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