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Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52
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)...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751257/ https://www.ncbi.nlm.nih.gov/pubmed/29215575 http://dx.doi.org/10.3390/ijms18122655 |
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author | Chen, Chin-Chuan Huang, Ju-Sui Wang, Tong-Hong Kuo, Chen-Hsin Wang, Chia-Jen Wang, Shu-Huei Leu, Yann-Lii |
author_facet | Chen, Chin-Chuan Huang, Ju-Sui Wang, Tong-Hong Kuo, Chen-Hsin Wang, Chia-Jen Wang, Shu-Huei Leu, Yann-Lii |
author_sort | Chen, Chin-Chuan |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-5751257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-57512572018-01-08 Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 Chen, Chin-Chuan Huang, Ju-Sui Wang, Tong-Hong Kuo, Chen-Hsin Wang, Chia-Jen Wang, Shu-Huei Leu, Yann-Lii Int J Mol Sci Article 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. MDPI 2017-12-07 /pmc/articles/PMC5751257/ /pubmed/29215575 http://dx.doi.org/10.3390/ijms18122655 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Chen, Chin-Chuan Huang, Ju-Sui Wang, Tong-Hong Kuo, Chen-Hsin Wang, Chia-Jen Wang, Shu-Huei Leu, Yann-Lii Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 |
title | Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 |
title_full | Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 |
title_fullStr | Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 |
title_full_unstemmed | Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 |
title_short | Dihydrocoumarin, an HDAC Inhibitor, Increases DNA Damage Sensitivity by Inhibiting Rad52 |
title_sort | dihydrocoumarin, an hdac inhibitor, increases dna damage sensitivity by inhibiting rad52 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5751257/ https://www.ncbi.nlm.nih.gov/pubmed/29215575 http://dx.doi.org/10.3390/ijms18122655 |
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