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The regulation of DNA supercoiling across evolution
Protein Science ( IF 8 ) Pub Date : 2021-08-16 , DOI: 10.1002/pro.4171
Alexandre Duprey 1 , Eduardo A Groisman 1, 2
Affiliation  

DNA supercoiling controls a variety of cellular processes, including transcription, recombination, chromosome replication, and segregation, across all domains of life. As a physical property, DNA supercoiling alters the double helix structure by under- or over-winding it. Intriguingly, the evolution of DNA supercoiling reveals both similarities and differences in its properties and regulation across the three domains of life. Whereas all organisms exhibit local, constrained DNA supercoiling, only bacteria and archaea exhibit unconstrained global supercoiling. DNA supercoiling emerges naturally from certain cellular processes and can also be changed by enzymes called topoisomerases. While structurally and mechanistically distinct, topoisomerases that dissipate excessive supercoils exist in all domains of life. By contrast, topoisomerases that introduce positive or negative supercoils exist only in bacteria and archaea. The abundance of topoisomerases is also transcriptionally and post-transcriptionally regulated in domain-specific ways. Nucleoid-associated proteins, metabolites, and physicochemical factors influence DNA supercoiling by acting on the DNA itself or by impacting the activity of topoisomerases. Overall, the unique strategies that organisms have evolved to regulate DNA supercoiling hold significant therapeutic potential, such as bactericidal agents that target bacteria-specific processes or anticancer drugs that hinder abnormal DNA replication by acting on eukaryotic topoisomerases specialized in this process. The investigation of DNA supercoiling therefore reveals general principles, conserved mechanisms, and kingdom-specific variations relevant to a wide range of biological questions.

中文翻译:

DNA超螺旋在进化过程中的调控

DNA 超螺旋控制着生命各个领域的各种细胞过程,包括转录、重组、染色体复制和分离。作为一种物理特性,DNA 超螺旋通过欠缠绕或过缠绕来改变双螺旋结构。有趣的是,DNA 超螺旋的进化揭示了其在生命三个领域的特性和调控方面的相似性和差异。尽管所有生物体都表现出局部的、受限制的 DNA 超螺旋,但只有细菌和古细菌表现出不受限制的全局超螺旋。DNA 超螺旋是由某些细胞过程自然产生的,也可以被称为拓扑异构酶的酶改变。虽然结构和机制不同,但消除过多超螺旋的拓扑异构酶存在于生命的各个领域。相比之下,引入正或负超螺旋的拓扑异构酶仅存在于细菌和古细菌中。拓扑异构酶的丰度也以域特异性方式进行转录和转录后调节。类核相关蛋白、代谢物和理化因素通过作用于 DNA 本身或影响拓扑异构酶的活性来影响 DNA 超螺旋。总体而言,生物体进化出的调节DNA超螺旋的独特策略具有显着的治疗潜力,例如针对细菌特异性过程的杀菌剂或通过作用于专门参与该过程的真核拓扑异构酶来阻碍异常DNA复制的抗癌药物。因此,对 DNA 超螺旋的研究揭示了与广泛的生物学问题相关的一般原理、保守机制和界特异性变异。
更新日期:2021-09-16
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