A genome-wide screen of genes involved in cadmium tolerance in Schizosaccharomyces pombe
A genome-wide screen of genes involved in cadmium tolerance in Schizosaccharomyces pombe
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DOI：
10.1093/toxsci/kfn153
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发表时间：
2008-11-01
影响因子：
3.8
通讯作者：
Russell, Paul
中科院分区：
文献类型：
--
作者：
Kennedy, Patrick J.;Vashisht, Ajay A.;Russell, Paul
镉是一种世界范围内的环境毒物，会导致包括癌症在内的一系列人类疾病。应激反应性解毒机制可最大程度地减少镉对细胞的损伤。我们通过单独筛选裂殖酵母（裂殖酵母）单倍体缺失集合中的突变体来探索镉耐受性的遗传要求，以抑制在含镉琼脂生长介质上的生长。进一步测试了镉敏感突变体对氧化应激（过氧化氢）和渗透应激（氯化钾）的敏感性。在筛选的 2649 个突变体中，237 个对镉敏感，其中 168 个是镉特异性的。大多数以前不知道与镉耐受性有关。这237个基因代表了许多途径，包括硫酸盐同化、植物螯合素合成和运输、泛醌（辅酶Q10）生物合成、应激信号传导、细胞壁生物合成和细胞形态、基因表达和染色质重塑、液泡功能以及大分子的细胞内运输。泛醌生物合成突变体对镉高度敏感，但对过氧化氢仅轻度敏感，表明辅酶 Q10 在镉耐受性方面发挥着更大的作用，而不仅仅是作为抗氧化剂。这些突变体和其他几个突变体在接触镉时会变黄，表明硫化镉积累。这种表型有可能用作镉的生物标志物。与酿酒酵母单倍体缺失集合的可比筛选几乎没有重叠，表明这两种远缘相关的酵母利用显着不同的策略来应对镉胁迫。讨论了这些策略及其与人体镉解毒的关系。
Cadmium is a worldwide environmental toxicant responsible for a range of human diseases including cancer. Cellular injury from cadmium is minimized by stress-responsive detoxification mechanisms. We explored the genetic requirements for cadmium tolerance by individually screening mutants from the fission yeast (Schizosaccharomyces pombe) haploid deletion collection for inhibited growth on agar growth media containing cadmium. Cadmium-sensitive mutants were further tested for sensitivity to oxidative stress (hydrogen peroxide) and osmotic stress (potassium chloride). Of 2649 mutants screened, 237 were sensitive to cadmium, of which 168 were cadmium specific. Most were previously unknown to be involved in cadmium tolerance. The 237 genes represent a number of pathways including sulfate assimilation, phytochelatin synthesis and transport, ubiquinone (Coenzyme Q10) biosynthesis, stress signaling, cell wall biosynthesis and cell morphology, gene expression and chromatin remodeling, vacuole function, and intracellular transport of macromolecules. The ubiquinone biosynthesis mutants are acutely sensitive to cadmium but only mildly sensitive to hydrogen peroxide, indicating that Coenzyme Q10 plays a larger role in cadmium tolerance than just as an antioxidant. These and several other mutants turn yellow when exposed to cadmium, suggesting cadmium sulfide accumulation. This phenotype can potentially be used as a biomarker for cadmium. There is remarkably little overlap with a comparable screen of the Saccharomyces cerevisiae haploid deletion collection, indicating that the two distantly related yeasts utilize significantly different strategies for coping with cadmium stress. These strategies and their relation to cadmium detoxification in humans are discussed.