PDF(Pubmed)
Abstract：
Topoisomerases regulate the topological state of cellular genomes to prevent impediments to vital cellular processes, including replication and transcription from suboptimal supercoiling of double-stranded DNA, and to untangle topological barriers generated as replication or recombination intermediates. The subfamily of type IA topoisomerases are the only topoisomerases that can alter the interlinking of both DNA and RNA. In this article, we provide a review of the mechanisms by which four highly conserved N-terminal protein domains fold into a toroidal structure, enabling cleavage and religation of a single strand of DNA or RNA. We also explore how these conserved domains can be combined with numerous non-conserved protein sequences located in the C-terminal domains to form a diverse range of type IA topoisomerases in Archaea, Bacteria, and Eukarya. There is at least one type IA topoisomerase present in nearly every free-living organism. The variation in C-terminal domain sequences and interacting partners such as helicases enable type IA topoisomerases to conduct important cellular functions that require the passage of nucleic acids through the break of a single-strand DNA or RNA that is held by the conserved N-terminal toroidal domains. In addition, this review will exam a range of human genetic disorders that have been linked to the malfunction of type IA topoisomerase.
摘要：
拓扑异构酶调节细胞基因组的拓扑状态，以防止阻碍重要的细胞过程，包括来自双链DNA次优超螺旋的复制和转录，并解开复制或重组中间体产生的拓扑屏障。IA型拓扑异构酶的亚家族是唯一可以改变DNA和RNA两者的互连的拓扑异构酶。在这篇文章中,我们对四个高度保守的N端蛋白结构域折叠成环形结构的机制进行了综述，能够切割和重新连接DNA或RNA的单链。我们还探索了这些保守结构域如何与位于C端结构域中的许多非保守蛋白质序列组合，以形成古菌中各种IA型拓扑异构酶。细菌,和Eukarya.在几乎每个自由生活的生物体中存在至少一种IA型拓扑异构酶。C末端结构域序列和相互作用配偶体(例如解旋酶)的变化使得IA型拓扑异构酶能够执行重要的细胞功能,其需要核酸通过由保守的N末端环形结构域保持的单链DNA或RNA的断裂而通过。此外,这篇综述将检查一系列与IA型拓扑异构酶功能异常相关的人类遗传疾病.
