| Autor: |
Miller KM; The Gurdon Institute, University of Cambridge, Cambridge, UK., Tjeertes JV, Coates J, Legube G, Polo SE, Britton S, Jackson SP |
| Jazyk: |
angličtina |
| Zdroj: |
Nature structural & molecular biology [Nat Struct Mol Biol] 2010 Sep; Vol. 17 (9), pp. 1144-51. Date of Electronic Publication: 2010 Aug 29. |
| DOI: |
10.1038/nsmb.1899 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
|
