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Inhibition of histone acetyltransferase activity by anacardic acid sensitizes tumor cells to ionizing radiation
Author(s) -
Sun Yingli,
Jiang Xiaofeng,
Chen Shujuan,
Price Brendan D.
Publication year - 2006
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2006.06.092
Subject(s) - histone acetyltransferase , histone acetyltransferases , dna damage , chromatin , chemistry , histone , acetylation , dna repair , cancer research , dna , ionizing radiation , microbiology and biotechnology , biochemistry , biology , gene , irradiation , physics , nuclear physics
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.