Inactivation of YAP1 enhances sensitivity of the yeast RNR3-lacZ genotoxicity testing system to a broad range of DNA-damaging agents.
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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DOI：
10.1093/toxsci/kfq391
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发表时间：
2011-04
期刊：
影响因子：
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通讯作者：
M. Zhang;Chao Zhang;Jia Li;Michelle D. Hanna;Xiaohua Zhang;Heping Dai;W. Xiao
中科院分区：
文献类型：
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作者：
M. Zhang;Chao Zhang;Jia Li;Michelle D. Hanna;Xiaohua Zhang;Heping Dai;W. Xiao
尽管使用基于微生物的遗传毒性测试系统来评估环境遗传毒性化合物取得了巨大进步，但大多数系统的反应很差，特别是对氧化剂。在本研究中，我们系统地检测了在活性氧保护方面存在缺陷的酿酒酵母突变株中的 RNR3-lacZ 报告基因表达，发现只有 YAP1 缺失才能显着增强氧化损伤的检测。令我们惊讶的是，YAP1 缺失还导致细胞对各种 DNA 损伤的敏感性增加。这种敏感性的改变似乎与氧化损伤无关，因为在维生素 C 治疗挽救氧化损伤的情况下，它无法逆转由其他类型的 DNA 损伤引起的表型。此外，虽然细胞通透性基因的失活增强了 RNR3-lacZ 检测灵敏度，特别是对大分子量化合物的灵敏度，但它们对小分子氧化剂的影响很小。总而言之，这项研究通过删除单个酵母基因，有助于创建一个针对多种 DNA 损伤剂的超敏遗传毒性测试系统。
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.