HDAC4 (green) and 53BP1 (red) colocalize in nuclear foci upon 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.

After 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.

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-...

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