State Key Laboratory of Microbial Metabolism, School of Life Science and Biotechnology, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Central Analytical lab, School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, Shanghai, People's Republic of China.
Sci Rep. 2017 Jun 14;7(1):3516. doi: 10.1038/s41598-017-02445-1.
DNA phosphorothioate (PT) modification is a sulfur modification on the backbone of DNA introduced by the proteins DndA-E. It has been detected within many bacteria isolates and metagenomic datasets, including human pathogens, and is considered to be widely distributed in nature. However, little is known about the physiological function of this modification, and thus its evolutionary significance and application potential remains largely a mystery. In this study, we focused on the advantages of DNA PT modification to bacterial cells coping with environmental stresses. We show that the mesophile Escherichia coli and the extremophile Shewanella piezotolerans both expanded their growth ranges following exposure to extreme temperature, salinity, pH, pressure, UV, X-ray and heavy metals as a result of DNA phophorothioation. The phophorothioated DNA reacted to both HO and hydroxyl radicals in vivo, and protected genomic DNA as well as sensitive enzymes from intracellular oxidative damage. We further demonstrate that this process has evolved separate from its associated role in DNA restriction and modification. These findings provide a physiological role for a covalent modification widespread in nature and suggest possible applications in biotechnology and biomedicine.
DNA 硫代磷酸酯（PT）修饰是由 DndA-E 蛋白在 DNA 骨架上引入的硫修饰。它已在许多细菌分离株和宏基因组数据集（包括人类病原体）中被检测到，被认为在自然界中广泛分布。然而，人们对这种修饰的生理功能知之甚少，因此其进化意义和应用潜力在很大程度上仍是一个谜。在这项研究中，我们专注于 DNA PT 修饰对细菌细胞应对环境压力的优势。我们表明，嗜温菌大肠杆菌和极端嗜热菌希瓦氏菌在暴露于极端温度、盐度、pH 值、压力、UV、X 射线和重金属后，由于 DNA 硫代磷酸化，其生长范围扩大了。体内的硫代磷酸化 DNA 与 HO 和羟基自由基反应，并保护基因组 DNA 以及敏感酶免受细胞内氧化损伤。我们进一步证明，这个过程是从其在 DNA 限制和修饰中的相关作用中独立进化而来的。这些发现为自然界中广泛存在的共价修饰提供了一种生理作用，并为生物技术和生物医学提供了可能的应用。
