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对缺失突变体进行全基因组规模筛选以深入了解对汞离子耐受性的分子机制

Genome-Scale Screening of Deletion Mutants to Gain Molecular Insight into Tolerance to Mercury Ions.

作者信息

Xian Jianing, Ni Leilei, Liu Chengkun, Li Jiyang, Cao Yuhang, Qin Jie, Liu Dongwu, Wang Xue

机构信息

School of Life Sciences and Medicine, Shandong University of Technology, Zibo 255049, China.

出版信息

J Fungi (Basel). 2024 Jul 16;10(7):492. doi: 10.3390/jof10070492.

Abstract

Mercury (Hg) is a global pollutant and a bioaccumulative toxin that seriously affects the environment. Though increasing information has been obtained on the mechanisms involved in mercury toxicity, there is still a knowledge gap between the adverse effects and action mechanisms, especially at the molecular level. In the current study, we screened a diploid library of single-gene deletion mutants to identify the nonessential genes associated with increased sensitivity to mercury ions. By genome-scale screening, we identified 64 yeast single-gene deletion mutants. These genes are involved in metabolism, transcription, antioxidant activity, cellular transport, transport facilitation, transport routes, and the cell cycle, as well as in protein synthesis, folding, modification, and protein destination. The concentration of mercury ions was different in the cells of yeast deletion mutants. Moreover, the disruption of antioxidant systems may play a key role in the mercurial toxic effects. The related functions of sensitive genes and signal pathways were further analyzed using bioinformatics-related technologies. Among 64 sensitive genes, 37 genes have human homologous analogs. Our results may provide a meaningful reference for understanding the action mode, cellular detoxification, and molecular regulation mechanisms of mercury toxicity.

摘要

汞(Hg)是一种全球性污染物和具有生物累积性的毒素,严重影响环境。尽管关于汞毒性所涉及的机制已获得越来越多的信息,但在不良影响与作用机制之间仍存在知识空白,尤其是在分子水平上。在本研究中,我们筛选了一个单基因缺失突变体的二倍体文库,以鉴定与对汞离子敏感性增加相关的非必需基因。通过全基因组规模筛选,我们鉴定出64个酵母单基因缺失突变体。这些基因参与代谢、转录、抗氧化活性、细胞运输、运输促进、运输途径和细胞周期,以及蛋白质合成、折叠、修饰和蛋白质定位。酵母缺失突变体细胞中的汞离子浓度有所不同。此外,抗氧化系统的破坏可能在汞的毒性作用中起关键作用。利用生物信息学相关技术进一步分析了敏感基因和信号通路的相关功能。在64个敏感基因中,有37个基因具有人类同源类似物。我们的结果可能为理解汞毒性的作用模式、细胞解毒和分子调控机制提供有意义的参考。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ed48/11277898/1022eddda6f3/jof-10-00492-g001.jpg

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