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首页> 外文期刊>Genomics >A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity.
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A genome-wide screen in Saccharomyces cerevisiae reveals pathways affected by arsenic toxicity.

机译：酿酒酵母中的全基因组筛选揭示了受砷毒性影响的途径。

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摘要

We have used Saccharomyces cerevisiae to identify toxicologically important proteins and pathways involved in arsenic-induced toxicity and carcinogenicity in humans. We performed a systemic screen of the complete set of 4733 haploid S. cerevisiae single-gene-deletion mutants to identify those that have decreased or increased growth, relative to wild type, after exposure to sodium arsenite (NaAsO(2)). IC(50) values for all mutants were determined to further validate our results. Ultimately we identified 248 mutants sensitive to arsenite and 5 mutants resistant to arsenite exposure. We analyzed the proteins corresponding to arsenite-sensitive mutants and determined that they belonged to functional categories that include protein binding, phosphate metabolism, vacuolar/lysosomal transport, protein targeting, sorting, and translocation, cell growth/morphogenesis, cell polarity and filament formation. Furthermore, these data were mapped onto a protein interactome to identify arsenite-toxicity-modulating networks. These networks are associated with the cytoskeleton, ubiquitination, histone acetylation and the MAPK signaling pathway. Our studies have potential implications for understanding toxicity and carcinogenesis in arsenic-induced human conditions, such as cancer and aging.
机译：我们已经使用了酿酒酵母来鉴定具有毒理学意义的重要蛋白和途径，这些蛋白和途径涉及砷对人的毒性和致癌性。我们对全套4733单倍体酿酒酵母单基因缺失突变体进行了系统的筛选，以鉴定那些暴露于亚砷酸钠（NaAsO（2））后相对于野生型而言具有减少或增加的生长的突变体。确定所有突变体的IC（50）值，以进一步验证我们的结果。最终，我们确定了248个对亚砷酸盐敏感的突变体和5个对砷暴露有抵抗力的突变体。我们分析了与砷敏感突变体相对应的蛋白质，并确定它们属于功能类别，包括蛋白质结合，磷酸盐代谢，液泡/溶酶体运输，蛋白质靶向，分类和易位，细胞生长/形态发生，细胞极性和细丝形成。此外，将这些数据映射到蛋白质相互作用组上，以鉴定砷毒毒性调节网络。这些网络与细胞骨架，泛素化，组蛋白乙酰化和MAPK信号通路相关。我们的研究对于理解砷引起的人类疾病（如癌症和衰老）中的毒性和致癌作用具有潜在的意义。

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