title: Inactivation of YAP1 enhances sensitivity of the yeast RNR3-lacZ genotoxicity testing system to a broad range of DNA-damaging agents.
abstract: 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.
authors.affiliation: Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei, 430072, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.forename: Michelle
authors.initials: M
authors.lastname: Hanna
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Zhang
authors.forename: Heping
authors.initials: H
authors.lastname: Dai
authors.forename: Wei
authors.initials: W
authors.lastname: Xiao
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D004249:DNA Damage; D004271:DNA, Fungal / Q000187:drug effects* / Q000528:radiation effects; D017353:Gene Deletion; D007763:Lac Operon; D009152:Mutagenicity Tests / Q000379:methods; D009153:Mutagens / Q000633:toxicity*; D010957:Plasmids; D017382:Reactive Oxygen Species / Q000378:metabolism; D012262:Ribonucleoside Diphosphate Reductase / Q000235:genetics*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D014466:Ultraviolet Rays; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D009153:Mutagens; D017382:Reactive Oxygen Species; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C086677:YAP1 protein, S cerevisiae; C517042:RNR3 protein, S cerevisiae; D012262:Ribonucleoside Diphosphate Reductase; D001616:beta-Galactosidase; D001205:Ascorbic Acid