Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52
AbstractEffective 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. View Full-Text
Share & Cite This Article
Chen, C.-C.; Huang, J.-S.; Wang, T.-H.; Kuo, C.-H.; Wang, C.-J.; Wang, S.-H.; Leu, Y.-L. Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52. Int. J. Mol. Sci. 2017, 18, 2655.
Chen C-C, Huang J-S, Wang T-H, Kuo C-H, Wang C-J, Wang S-H, Leu Y-L. Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52. International Journal of Molecular Sciences. 2017; 18(12):2655.Chicago/Turabian Style
Chen, Chin-Chuan; Huang, Ju-Sui; Wang, Tong-Hong; Kuo, Chen-Hsin; Wang, Chia-Jen; Wang, Shu-Huei; Leu, Yann-Lii. 2017. "Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52." Int. J. Mol. Sci. 18, no. 12: 2655.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.