Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes

CORC > 水生生物研究所 > 中科院水生所知识产出（2009年前） > 水生生物分子与细胞生物学研究中心 > 期刊论文

	Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes
	Zhang, Min 2; Hanna, Michelle 1; Li, Jia 1; Butcher, Susan 1; Dai, Heping 2; Xiao, Wei 1
刊名	TOXICOLOGICAL SCIENCES
	2010-02-01
卷号	113 期号:2 页码:401-411
关键词	Saccharomyces cerevisiae RNR3-lacZ genotoxicity test permeability ABC transporters cell wall
ISSN号	1096-6080
通讯作者	Xiao, W, Univ Saskatchewan, Dept Microbiol & Immunol, 107 Wiggins Rd, Saskatoon, SK S7N 5E5, Canada
中文摘要	We previously established a genotoxicity detection system based on the transcriptional response of the yeast RNR3 gene to DNA damage. In order to further improve its sensitivity to genotoxicants, we have attempted to increase cell permeability by removing cell wall mannoproteins (CWPs). Here, we report that selected deletion of pleiotropic drug resistance (PDR) genes encoding membrane efflux transporters also enhanced cellular sensitivity to treatment by various genotoxic agents. Furthermore, we have validated our hypothesis that PDR and CWP protect cells through different mechanisms by demonstrating that simultaneous inactivation of the above two pathways resulted in a synergistic enhancement of assay sensitivity as measured by RNR3-lacZ expression and that this effect is at the cell permeability level. The quadruple mutation results in RNR3-lacZ assay sensitivity to tested chemicals that apparently surpasses the industry standard Ames test. We argue that this hyperpermeable yeast mutant strain would be suitable for other chemical-based genotoxic assays.
英文摘要	We previously established a genotoxicity detection system based on the transcriptional response of the yeast RNR3 gene to DNA damage. In order to further improve its sensitivity to genotoxicants, we have attempted to increase cell permeability by removing cell wall mannoproteins (CWPs). Here, we report that selected deletion of pleiotropic drug resistance (PDR) genes encoding membrane efflux transporters also enhanced cellular sensitivity to treatment by various genotoxic agents. Furthermore, we have validated our hypothesis that PDR and CWP protect cells through different mechanisms by demonstrating that simultaneous inactivation of the above two pathways resulted in a synergistic enhancement of assay sensitivity as measured by RNR3-lacZ expression and that this effect is at the cell permeability level. The quadruple mutation results in RNR3-lacZ assay sensitivity to tested chemicals that apparently surpasses the industry standard Ames test. We argue that this hyperpermeable yeast mutant strain would be suitable for other chemical-based genotoxic assays.
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]	PROMOTER-REPORTER CONSTRUCT ; SACCHAROMYCES-CEREVISIAE ; MULTIDRUG-RESISTANCE ; DNA-DAMAGE ; PLEIOTROPIC DRUG ; TRANSCRIPTIONAL CONTROL ; ABC TRANSPORTERS ; TESTING SYSTEM ; IN-VIVO ; SENSITIVITY
收录类别	SCI
资助信息	Natural Science Foundation of China [30440420603]; Natural Sciences and Engineering Research Council of Canada [138338]; Chinese National Key Laboratory FEBT [2008FB002]
语种	英语
WOS记录号	WOS:000273706200014
公开日期	2010-12-23
内容类型	期刊论文
源URL	[http://ir.ihb.ac.cn/handle/342005/13755]
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 Hydrol, Wuhan 430072, Hubei, Peoples R China
推荐引用方式 GB/T 7714	Zhang, Min,Hanna, Michelle,Li, Jia,et al. Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes[J]. TOXICOLOGICAL SCIENCES,2010,113(2):401-411.
APA	Zhang, Min,Hanna, Michelle,Li, Jia,Butcher, Susan,Dai, Heping,&Xiao, Wei.(2010).Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes.TOXICOLOGICAL SCIENCES,113(2),401-411.
MLA	Zhang, Min,et al."Creation of a Hyperpermeable Yeast Strain to Genotoxic Agents through Combined Inactivation of PDR and CWP Genes".TOXICOLOGICAL SCIENCES 113.2(2010):401-411.