Journal Article

Inactivation of <i>YAP1</i> Enhances Sensitivity of the Yeast <i>RNR3-lacZ</i> Genotoxicity Testing System to a Broad Range of DNA-Damaging Agents

Min Zhang, Chao Zhang, Jia Li, Michelle Hanna, Xiaohua Zhang, Heping Dai and Wei Xiao

in Toxicological Sciences

Volume 120, issue 2, pages 310-321
Published in print April 2011 | ISSN: 1096-6080
Published online December 2010 | e-ISSN: 1096-0929 | DOI:
Inactivation of YAP1 Enhances Sensitivity of the Yeast RNR3-lacZ Genotoxicity Testing System to a Broad Range of DNA-Damaging Agents

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Despite the great advances by using microorganism-based genotoxicity testing systems to assess environmental genotoxic compounds, most of them respond poorly, particularly to oxidative agents. In this study, we systematically examined the RNR3-lacZ reporter gene expression in Saccharomyces cerevisiae mutant strains defective in the protection against reactive oxygen species and found that only YAP1 deletion resulted in a significant enhancement in the detection of oxidative damage. To our surprise, YAP1 deletion also caused an increased cellular sensitivity to a variety of DNA damage. This altered sensitivity appears to be independent of oxidative damage because under conditions in which vitamin C treatment rescued oxidative damage, it failed to reverse the phenotypes caused by other types of DNA damage. Furthermore, although inactivation of cell permeability genes enhanced the RNR3-lacZ detection sensitivity particularly to large molecular weight compounds, their effects on small molecular oxidative agents are minimal. Taken together, this study helps to create a hypersensitive genotoxicity testing system to a broad range of DNA-damaging agents by deleting a single yeast gene.

Keywords: RNR3-lacZ; yeast; oxidative compounds; YAP1; genotoxicity test; sensitivity

Journal Article.  6166 words.  Illustrated.

Subjects: Medical Toxicology ; Toxicology (Non-medical)

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