Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress
Comparative Genomic Screen in Two Yeasts Reveals Conserved Pathways in the Response Network to Phenol Stress
复制标题
两种酵母的比较基因组筛选揭示了苯酚应激反应网络中的保守途径
DOI：
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发表时间：
2019
期刊：
影响因子：
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通讯作者：
Zhaouhua Tang
中科院分区：
文献类型：
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作者：
Bashar Alhoch;Alan Chen;Elaine Chan;Asmaa Elkabti;S. Fariña;Catherine H Gilbert;Jea;Bradley King;K. Leung;Julia Levy;Elizabeth Martin;Benjamin Mazer;Sara McKinney;Alexandra G. Moyzis;Margaret Nurimba;M. Ozaki;Kathleen L. Purvis;Joshua M Rothman;S. Raju;C. Selassie;Oliver Smith;Julia Ticus;G. Edwalds;M. C. Negritto;Ruye Wang;Zhaouhua Tang
生物体会遇到各种扰动，对这些扰动的反应机制对物种的生存至关重要。有缺陷的应激反应与许多人类疾病有关，包括癌症和神经退行性疾病。苯酚衍生物，天然存在的和合成的，显示有益的以及有害的影响。本研究中的苯酚衍生物，丁基羟基茴香醚（BHA），丁基羟基甲苯（BHT）和双酚A（BPA），广泛用作食品防腐剂和工业化学品。已经报告了关于其生物活性和与疾病发展相关性的验证结果;了解苯酚作用的分子基础是解决与人类健康相关问题的关键步骤。这项工作提出了第一个比较基因组分析的苯酚胁迫反应的遗传网络中的两个不同的酵母，粟酒裂殖酵母和酿酒酵母的进化背景。两种酵母的缺失菌株文库的基因组筛选鉴定了细胞对苯酚应激反应所需的基因，这些基因在人类直系同源物中富集。对这些基因的功能分析揭示了所涉及的主要信号通路。这些结果提供了一个全球性的生物事件构成的防御过程，包括细胞周期阻滞，DNA修复，苯酚解毒V-ATP酶，活性氧缓解，内质网应激缓解通过麦角固醇和未折叠蛋白质的反应，揭示这些细胞通路的新角色。
Living organisms encounter various perturbations, and response mechanisms to such perturbations are vital for species survival. Defective stress responses are implicated in many human diseases including cancer and neurodegenerative disorders. Phenol derivatives, naturally occurring and synthetic, display beneficial as well as detrimental effects. The phenol derivatives in this study, butylated hydroxyanisole (BHA), butylated hydroxytoluene (BHT), and bisphenol A (BPA), are widely used as food preservatives and industrial chemicals. Conflicting results have been reported regarding their biological activity and correlation with disease development; understanding the molecular basis of phenol action is a key step for addressing issues relevant to human health. This work presents the first comparative genomic analysis of the genetic networks for phenol stress response in an evolutionary context of two divergent yeasts, Schizosaccharomyces pombe and Saccharomyces cerevisiae. Genomic screening of deletion strain libraries of the two yeasts identified genes required for cellular response to phenol stress, which are enriched in human orthologs. Functional analysis of these genes uncovered the major signaling pathways involved. The results provide a global view of the biological events constituting the defense process, including cell cycle arrest, DNA repair, phenol detoxification by V-ATPases, reactive oxygen species alleviation, and endoplasmic reticulum stress relief through ergosterol and the unfolded protein response, revealing novel roles for these cellular pathways.
影响因子：
19
作者：
Chen, Yani;Brandizzi, Federica
通讯作者：
Brandizzi, Federica