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

被引：507

作者：

Miller, Kyle M. ^{[1
]}

Tjeertes, Jorrit V. ^{[1
]}

Coates, Julia ^{[1
]}

Legube, Gaelle ^{[2
,3
]}

Polo, Sophie E. ^{[1
]}

Britton, Sebastien ^{[1
]}

Jackson, Stephen P. ^{[1
]}

机构：

[1] Univ Cambridge, Gurdon Inst, Cambridge, England

[2] Univ Toulouse, Toulouse, France

[3] Ctr Natl Rech Sci, Lab Biol Cellulaire & Mol Controle Proliferat, Toulouse, France

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 09期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会;

关键词：

DOUBLE-STRAND BREAKS; HISTONE DEACETYLASE INHIBITORS; ACETYLATION; REPAIR; CHECKPOINT; SENESCENCE; CHROMATIN; H3; GAMMA-H2AX; P53;

D O I：

10.1038/nsmb.1899

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1144 / U15

页数：9

共 46 条

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