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Int. J. Mol. Sci. 2017, 18(12), 2655; https://doi.org/10.3390/ijms18122655

Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52

1
Graduate Institute of Natural Products, Chang Gung University, Taoyuan 333, Taiwan
2
Tissue Bank, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
3
Chinese Herbal Medicine Research Team, Healthy Aging Research Center, Chang Gung University, Taoyuan 333, Taiwan
4
Graduate Institute of Health Industry Technology, Research Center for Industry of Human Ecology, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan 333, Taiwan
5
Liver Research Center, Chang Gung Memorial Hospital, Linko 333, Taiwan
6
Institute of Stem Cell and Translational Cancer Research, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
7
Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, Taipei 100, Taiwan
8
Center for Traditional Chinese Medicine, Chang Gung Memorial Hospital, Taoyuan 333, Taiwan
*
Authors to whom correspondence should be addressed.
Received: 13 November 2017 / Revised: 1 December 2017 / Accepted: 5 December 2017 / Published: 7 December 2017
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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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. View Full-Text
Keywords: yeast; DSB; DHC; DNA damage sensitivity; homologous recombination; Rad52 yeast; DSB; DHC; DNA damage sensitivity; homologous recombination; Rad52
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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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.

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