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FEBS Lett. 2006 Aug 7;580(18):4353-6. Epub 2006 Jul 10.

Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation.

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Department of Radiation Oncology, Division of Genomic Stability and DNA Repair, Harvard Medical School, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115, USA.


Histone acetyltransferases (HATs) regulate transcription, chromatin structure and DNA repair. Here, we utilized a novel HAT inhibitor, anacardic acid, to examine the role of HATs in the DNA damage response. Anacardic acid inhibits the Tip60 HAT in vitro, and blocks the Tip60-dependent activation of the ATM and DNA-PKcs protein kinases by DNA damage in vivo. Further, anacardic acid sensitizes human tumor cells to the cytotoxic effects of ionizing radiation. These results demonstrate a central role for HATs such as Tip60 in regulating the DNA damage response. HAT inhibitors provide a novel therapeutic approach for increasing the sensitivity of tumors to radiation therapy.

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