Institut de Génétique Humaine (IGH), Centre National de la Recherche Scientifique, Univ Montpellier, Montpellier 34396, France.
Max Planck Institute for Developmental Biology, Tübingen 72076, Germany.
Mol Biol Evol. 2022 Nov 3;39(11). doi: 10.1093/molbev/msac227.
Type II DNA topoisomerases regulate topology by double-stranded DNA cleavage and ligation. The TopoVI family of DNA topoisomerase, first identified and biochemically characterized in Archaea, represents, with TopoVIII and mini-A, the type IIB family. TopoVI has several intriguing features in terms of function and evolution. TopoVI has been identified in some eukaryotes, and a global view is lacking to understand its evolutionary pattern. In addition, in eukaryotes, the two TopoVI subunits (TopoVIA and TopoVIB) have been duplicated and have evolved to give rise to Spo11 and TopoVIBL, forming TopoVI-like (TopoVIL), a complex essential for generating DNA breaks that initiate homologous recombination during meiosis. TopoVIL is essential for sexual reproduction. How the TopoVI subunits have evolved to ensure this meiotic function is unclear. Here, we investigated the phylogenetic conservation of TopoVI and TopoVIL. We demonstrate that BIN4 and RHL1, potentially interacting with TopoVIB, have co-evolved with TopoVI. Based on model structures, this observation supports the hypothesis for a role of TopoVI in decatenation of replicated chromatids and predicts that in eukaryotes the TopoVI catalytic complex includes BIN4 and RHL1. For TopoVIL, the phylogenetic analysis of Spo11, which is highly conserved among Eukarya, highlighted a eukaryal-specific N-terminal domain that may be important for its regulation. Conversely, TopoVIBL was poorly conserved, giving rise to ATP hydrolysis-mutated or -truncated protein variants, or was undetected in some species. This remarkable plasticity of TopoVIBL provides important information for the activity and function of TopoVIL during meiosis.
II 型 DNA 拓扑异构酶通过双链 DNA 的切割和连接来调节拓扑结构。拓扑异构酶 VI 家族首先在古菌中被发现并进行了生化特征鉴定，它与拓扑异构酶 VIII 和 mini-A 一起构成了 IIB 家族。拓扑异构酶 VI 在功能和进化方面具有一些引人注目的特征。拓扑异构酶 VI 已在一些真核生物中被鉴定出来，但缺乏全面的了解来理解其进化模式。此外，在真核生物中，拓扑异构酶 VI 的两个亚基（拓扑异构酶 VI A 和拓扑异构酶 VI B）已经被复制，并进化为 Spo11 和拓扑异构酶 VI B 样（TopoVIBL），形成拓扑异构酶 VI 样（TopoVIL）复合物，该复合物对于产生在减数分裂中起始同源重组的 DNA 断裂是必不可少的。TopoVIL 对于有性生殖是必不可少的。拓扑异构酶 VI 亚基如何进化以确保这种减数分裂功能尚不清楚。在这里，我们研究了拓扑异构酶 VI 和 TopoVIL 的系统发育保守性。我们证明，与拓扑异构酶 VI B 潜在相互作用的 BIN4 和 RHL1 与 TopoVI 共同进化。基于模型结构，这一观察结果支持了拓扑异构酶 VI 在复制的染色单体解缠结中的作用假说，并预测在真核生物中，拓扑异构酶 VI 的催化复合物包括 BIN4 和 RHL1。对于 TopoVIL，在真核生物中高度保守的 Spo11 的系统发育分析突出了一个可能对其调节很重要的真核生物特异性 N 端结构域。相反，TopoVIBL 保守性较差，导致 ATP 水解突变或截断的蛋白质变体，或者在一些物种中未检测到。TopoVIBL 的这种显著的可塑性为 TopoVIL 在减数分裂中的活性和功能提供了重要信息。
