The road less traveled: A new phosphorothioate antiviral defense mechanism discovered in Archaea
The road less traveled: A new phosphorothioate antiviral defense mechanism discovered in Archaea
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DOI：
10.1016/j.synbio.2019.06.002
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发表时间：
2019-06
影响因子：
4.8
通讯作者：
M. DeMott;P. Dedon
中科院分区：
文献类型：
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作者：
M. DeMott;P. Dedon
DNA硫代修饰的故事开始于50多年前，就像弗罗斯特在森林中的漫步一样展开。1970年，弗里茨·埃克斯坦合成了寡核苷酸，其中磷酸二酯主链上的非桥氧被硫取代，硫是第一个硫代修饰的核酸[2]。20年后，邓紫欣和他的同事在拥有5个基因DND簇的细菌中发现了DNA降解表型，并通过在细菌基因组中掺入硫而导致凝胶降解[3]。20年后，随着王等人的发现，这些化学和生物之路再次相遇。DND蛋白将硫作为硫化物插入不同细菌的基因组中[4]。作为一种表观遗传标记，硫代磷酸盐最早的功能作用是在限制修饰“免疫监视”中被确定，修饰由DND蛋白ABCDE和DndFGH调节，执行对未标记的外源DNA的限制切割[5]。但DND簇的行为并不像典型的基于甲基化的限制-修改系统，它修改了基因组中所有共同的位点。下一代测序的进步促进了硫代磷的基因组图谱的绘制，这表明只有10%-15%的短共有序列(如CPSCA、GPSTTC/GPSAAC)被修改，在基因组的双链位置频繁地进行部分修改[6]。除了限制修饰，硫代磷酸盐在调节基因表达、细胞代谢和氧化应激反应方面已经出现了新的功能[7，8]。随着行走的快速进行，最近熊等人的发现发生了急剧的转折，硫代磷酸DNA修饰的故事发生了急剧转变。在古生代发现了一种全新的基于硫代磷的抗病毒防御系统[9]。古生菌微生物学的研究不如细菌的研究，这导致了熊等人的研究。探索硫代磷酸盐
The story of phosphorothioate modifications of DNA begins over 50 years ago and has unfolded like Frost's walk in the woods [1]. In 1970, Fritz Eckstein synthesized oligonucleotides in which a non-bridging oxygen in the phosphodiester backbone was replaced by sulfur–the first phosphorothioate-modified nucleic acid [2]. Twenty years passed until Zixin Deng and colleagues discovered a DNA degradation phenotype in bacteria possessing a 5-gene dnd cluster, with electrophoretic degradation caused by incorporation of sulfur into bacterial genomes [3]. These roads of chemistry and biology met again another 20 years later with the discovery by Wang et al. that Dnd proteins insert sulfur as a phosphorothioate in the genomes of diverse bacteria [4]. This walk in the woods now picked up speed.As an epigenetic mark, the earliest functional role for phosphorothioates was identified in restriction-modification “immune surveillance”, with modification regulated by Dnd proteins ABCDE and DndFGH performing the restriction cleavage of unmarked foreign DNA [5]. But the dnd cluster did not behave like a typical methylation-based restriction-modification system, with modification of all consensus sites in a genome. Advancements in next generation sequencing facilitated genomic mapping of phosphorothioates, which revealed that only∼ 10–15% of short consensus sequences (eg, CPSCA, GPSTTC/GPSAAC) were modified, with frequent partial modification at bistranded sites on the genome [6]. Beyond restriction-modification, new functions have emerged for phosphorothioates in regulating gene expression, cellular metabolism, and oxidative stress response [7, 8]. With the walk moving at a rapid pace, the story of phosphorothioate DNA modifications recently took a sharp turn in the discovery by Xiong et al. of a completely new phosphorothioate-based anti-viral defense system in Archaea [9]. Archaeal microbiology is not as well studied as that of bacteria, which led Xiong et al. to explore phosphorothioate