拓扑异构酶 VIB 样蛋白家族对于减数分裂 DNA 双链断裂的形成是必需的。
The TopoVIB-Like protein family is required for meiotic DNA double-strand break formation.
机构信息
Institute of Human Genetics, UPR 1142 CNRS, 141 Rue de la Cardonille, 34396 Montpellier cedex 05, France.
Centre de Biologie du Développement, Université Fédérale de Toulouse, Paul Sabatier Campus, 118 Route de Narbonne, 31062 Toulouse, France.
出版信息
Science. 2016 Feb 26;351(6276):943-9. doi: 10.1126/science.aad5309.
Meiotic recombination is induced by the formation of DNA double-strand breaks (DSBs) catalyzed by SPO11, the ortholog of subunit A of TopoVI DNA topoisomerase (TopoVIA). TopoVI activity requires the interaction between A and B subunits. We identified a conserved family of plant and animal proteins [the TOPOVIB-Like (TOPOVIBL) family] that share strong structural similarity to the TopoVIB subunit of TopoVI DNA topoisomerase. We further characterize the meiotic recombination proteins Rec102 (Saccharomyces cerevisiae), Rec6 (Schizosaccharomyces pombe), and MEI-P22 (Drosophila melanogaster) as homologs to the transducer domain of TopoVIB. We demonstrate that the mouse TOPOVIBL protein interacts and forms a complex with SPO11 and is required for meiotic DSB formation. We conclude that meiotic DSBs are catalyzed by a complex involving SPO11 and TOPOVIBL.
减数分裂重组是由 SPO11 催化的 DNA 双链断裂（DSBs）诱导的，SPO11 是 TopoVI DNA 拓扑异构酶亚基 A（TopoVIA）的同源物。TopoVI 的活性需要 A 和 B 亚基之间的相互作用。我们鉴定了一个保守的植物和动物蛋白家族[TOPOVIB 样（TOPOVIBL）家族]，它们与 TopoVI DNA 拓扑异构酶的 TopoVIB 亚基具有很强的结构相似性。我们进一步将减数分裂重组蛋白 Rec102（酿酒酵母）、Rec6（裂殖酵母）和 MEI-P22（黑腹果蝇）鉴定为 TopoVIB 转导结构域的同源物。我们证明，小鼠 TOPOVIBL 蛋白与 SPO11 相互作用并形成复合物，并且是减数分裂 DSB 形成所必需的。我们的结论是，减数分裂 DSB 是由涉及 SPO11 和 TOPOVIBL 的复合物催化的。
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