期刊
FEBS LETTERS
卷 580, 期 18, 页码 4353-4356出版社
WILEY
DOI: 10.1016/j.febslet.2006.06.092
关键词
ATM; anacardic acid; Tip60; HAT; radiosensitivity; DNA repair
资金
- NINDS NIH HHS [R21 NS061669] Funding Source: Medline
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. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
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