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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	Inactivation of YAP1 Enhances Sensitivity of the Yeast RNR3-lacZ Genotoxicity Testing System to a Broad Range of DNA-Damaging Agents
	Zhang, Min 2; Zhang, Chao 2; Li, Jia 1; Hanna, Michelle 1; Zhang, Xiaohua 2; Dai, Heping 2; Xiao, Wei 1
刊名	TOXICOLOGICAL SCIENCES
	2011-04-01
卷号	120 期号:2 页码:310-321
关键词	RNR3-lacZ yeast oxidative compounds YAP1 genotoxicity test sensitivity
ISSN号	1096-6080
通讯作者	Xiao, W, Univ Saskatchewan, Dept Microbiol & Immunol, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada ; wei.xiao@usask.ca
中文摘要	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.
英文摘要	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.
学科主题	Toxicology
WOS标题词	Science & Technology ; Life Sciences & Biomedicine
类目[WOS]	Toxicology
研究领域[WOS]	Toxicology
关键词[WOS]	TERT-BUTYL HYDROPEROXIDE ; SACCHAROMYCES-CEREVISIAE ; REACTIVE OXYGEN ; OXIDATIVE-STRESS ; TRANSCRIPTIONAL ACTIVATOR ; ESCHERICHIA-COLI ; VITAMIN-C ; CWP GENES ; REPAIR ; PROTECTION
收录类别	SCI
资助信息	Natural Science Foundation of China [20977108]; Natural Sciences and Engineering Research Council of Canada [OPG0138338]; State Key Laboratory of Freshwater Ecology and Biotechnology of China [2010FB03, 2009FBZ08]
语种	英语
WOS记录号	WOS:000288804800007
公开日期	2011-06-30
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/15670]
专题	水生生物研究所_水生生物分子与细胞生物学研究中心_期刊论文
作者单位	1.Univ Saskatchewan, Dept Microbiol & Immunol, Saskatoon, SK S7N 5E5, Canada 2.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Min,Zhang, Chao,Li, Jia,et al. Inactivation of YAP1 Enhances Sensitivity of the Yeast RNR3-lacZ Genotoxicity Testing System to a Broad Range of DNA-Damaging Agents[J]. TOXICOLOGICAL SCIENCES,2011,120(2):310-321.
APA	Zhang, Min.,Zhang, Chao.,Li, Jia.,Hanna, Michelle.,Zhang, Xiaohua.,...&Xiao, Wei.(2011).Inactivation of YAP1 Enhances Sensitivity of the Yeast RNR3-lacZ Genotoxicity Testing System to a Broad Range of DNA-Damaging Agents.TOXICOLOGICAL SCIENCES,120(2),310-321.
MLA	Zhang, Min,et al."Inactivation of YAP1 Enhances Sensitivity of the Yeast RNR3-lacZ Genotoxicity Testing System to a Broad Range of DNA-Damaging Agents".TOXICOLOGICAL SCIENCES 120.2(2011):310-321.