|Title:||Curcumin-mediated HDAC inhibition suppresses the DNA damage response and contributes to increased DNA damage sensitivity||Authors:||SHU-HUEI WANG
|Issue Date:||2015||Publisher:||Public Library of Science||Journal Volume:||10||Journal Issue:||7||Start page/Pages:||e0134110||Source:||PLoS ONE||Abstract:||
Chemo-and radiotherapy cause multiple forms of DNA damage and lead to the death of cancer cells. Inhibitors of the DNA damage response are candidate drugs for use in combination therapies to increase the efficacy of such treatments. In this study, we show that curcumin, a plant polyphenol, sensitizes budding yeast to DNA damage by counteracting the DNA damage response. Following DNA damage, the Mec1-dependent DNA damage checkpoint is inactivated and Rad52 recombinase is degraded by curcumin, which results in deficiencies in double-stand break repair. Additive effects on damage-induced apoptosis and the inhibition of damage-induced autophagy by curcumin were observed. Moreover, rpd3 mutants were found to mimic the curcumin-induced suppression of the DNA damage response. In contrast, hat1 mutants were resistant to DNA damage, and Rad52 degradation was impaired following curcumin treatment. These results indicate that the histone deacetylase inhibitor activity of curcumin is critical to DSB repair and DNA damage sensitivity. Copyright: ? 2015 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
|ISSN:||1932-6203||DOI:||10.1371/journal.pone.0134110||metadata.dc.subject.other:||curcumin; histone deacetylase; Mec1 protein; phosphatidylinositol 3 kinase; Rad52 protein; unclassified drug; antineoplastic agent; curcumin; histone deacetylase; histone deacetylase inhibitor; apoptosis; Article; autophagy; controlled study; DNA damage; DNA repair; double stranded DNA break; down regulation; drug mechanism; enzyme degradation; enzyme inactivation; enzyme inhibition; G2 phase cell cycle checkpoint; nonhuman; protein expression; sensitivity analysis; sensitization; yeast cell; acetylation; cell cycle checkpoint; cell proliferation; chemistry; chromatin immunoprecipitation; DNA damage; drug effects; drug resistance; genetics; immunoblotting; metabolism; Saccharomyces cerevisiae; signal transduction; Acetylation; Antineoplastic Agents; Apoptosis; Cell Cycle Checkpoints; Cell Proliferation; Chromatin Immunoprecipitation; Curcumin; DNA Damage; DNA Repair; Drug Resistance; Histone Deacetylase Inhibitors; Histone Deacetylases; Immunoblotting; Saccharomyces cerevisiae; Signal Transduction
|Appears in Collections:||解剖學暨細胞生物學科所|
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