标题: Deacetylase undoes DNA damage [打印本页] 作者: 杨柳 时间: 2009-3-6 00:57 标题: Deacetylase undoes DNA damage
An article on page 1017 by Kao et al. connects histone modifying enzymes with double-stranded DNA repair mechanisms. The combination suggests a one–two punch that may improve a current cancer treatment.' F3 x7 E4 U! `* {" |
' H g: k" ?1 z6 p2 U) i) k- s- hAfter DNA damage caused by irradiation, various proteins accumulate at nuclear foci, where they recognize and repair double-stranded DNA breaks. Kao and colleagues found that, in human cells, some early forming foci contain the histone deacetylase HDAC4. The HDAC4 foci disappeared as DNA was repaired in cells competent for repair. However, in repair-impaired cells, HDAC4 foci persisted, suggesting that they may be a marker for strand breaks.5 a8 q( b8 O0 u6 a
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HDAC4 foci in irradiated cells also contained the p53-binding protein 53BP1, which was recently implicated in maintaining DNA damage–induced S and G2 checkpoints. Depletion of HDAC4 by RNA interference caused the loss of 53BP1. HDAC- depleted cells were highly sensitive to radiation and were unable to maintain the G2 checkpoint, probably as a result of losing 53BP1.HDAC inhibitors as single agent anticancer treatments have shown some promise in clinical trials. The results of Kao et al. suggest that HDAC inhibitors may be more effective when used in combination with DNA-damaging agents, as they may prevent subsequent repair mechanisms.(HDAC4 (green) and 53BP1 (red) colocalize)作者: 大小年 时间: 2015-6-2 12:43