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- Title
Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52.
- Authors
Chin-Chuan Chen; Ju-Sui Huang; Tong-Hong Wang; Chen-Hsin Kuo; Chia-Jen Wang; Shu-Huei Wang; Yann-Lii Leu
- Abstract
Effective DNA repair enables cancer cells to survive DNA damage induced by chemotherapeutic or radiotherapeutic treatments. Therefore, inhibiting DNA repair pathways is a promising therapeutic strategy for increasing the efficacy of such treatments. In this study, we found that dihydrocoumarin (DHC), a flavoring agent, causes deficiencies in double-stand break (DSB) repair and prolonged DNA damage checkpoint recovery in yeast. Following DNA damage, Rad52 recombinase was revealed to be inhibited by DHC, which results in deficiencies in DSB repair and prolonged DNA damage checkpoint recovery. The deletion of RPD3, a class I histone deacetylase (HDAC), was found to mimic DHC-induced suppression of Rad52 expression, suggesting that the HDAC inhibitor activity of DHC is critical to DSB repair and DNA damage sensitivity. Overall, our findings delineate the regulatory mechanisms of DHC in DSB repair and suggest that it might potentially be used as an inhibitor of the DNA repair pathway in human cells.
- Subjects
DNA repair; DNA damage; DOUBLE-strand DNA breaks; HISTONE deacetylase inhibitors; RECOMBINATION (Chemistry)
- Publication
International Journal of Molecular Sciences, 2017, Vol 18, Issue 12, p2655
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms18122655