https://scholars.lib.ntu.edu.tw/handle/123456789/467663
Title: | Dihydrocoumarin, an HDAC inhibitor, increases DNA damage sensitivity by inhibiting Rad52 | Authors: | Chen C.-C. Huang J.-S. Wang T.-H. Kuo C.-H. Wang C.-J. SHU-HUEI WANG Leu Y.-L. |
Issue Date: | 2017 | Publisher: | MDPI AG | Journal Volume: | 18 | Journal Issue: | 12 | Start page/Pages: | 2655 | Source: | International Journal of Molecular Sciences | 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. ? 2017 by the authors. Licensee MDPI, Basel, Switzerland. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-85037615103&doi=10.3390%2fijms18122655&partnerID=40&md5=e874ae6f56a59b9d4b6b7a7e47c6443b https://scholars.lib.ntu.edu.tw/handle/123456789/467663 |
ISSN: | 1661-6596 | DOI: | 10.3390/ijms18122655 | SDG/Keyword: | autophagy related protein 8 family; coumarin derivative; dihydrocoumarin; nocodazole; proteasome; Rad52 protein; unclassified drug; 3,4-dihydrocoumarin; coumarin derivative; flavoring agent; histone deacetylase inhibitor; Rad52 protein; RAD52 protein, S cerevisiae; Saccharomyces cerevisiae protein; apoptosis; Article; autophagy; cell cycle checkpoint; chromatin immunoprecipitation; colony formation; controlled study; DNA damage; double stranded DNA break; fluorescence microscopy; gene expression; homologous recombination; immunoblotting; multiplex polymerase chain reaction; nonhuman; propidium iodide assay; protein degradation; protein expression; protein processing; real time polymerase chain reaction; reverse transcription polymerase chain reaction; RNA extraction; single stranded DNA break; spectrophotometry; Western blotting; antagonists and inhibitors; drug effect; genetics; metabolism; recombination repair; Saccharomyces cerevisiae; Coumarins; DNA Damage; Flavoring Agents; Histone Deacetylase Inhibitors; Rad52 DNA Repair and Recombination Protein; Recombinational DNA Repair; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins |
Appears in Collections: | 解剖學暨細胞生物學科所 |
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