Tang Shangming, Wu Michelle Ka Yan, Zhang Ruoxi, Hunter Neil
Howard Hughes Medical Institute and the Departments of Microbiology & Molecular Genetics, Molecular & Cellular Biology and Cell Biology & Human Anatomy, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
Howard Hughes Medical Institute and the Departments of Microbiology & Molecular Genetics, Molecular & Cellular Biology and Cell Biology & Human Anatomy, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, USA.
Mol Cell. 2015 Feb 19;57(4):607-621. doi: 10.1016/j.molcel.2015.01.021.
The Bloom's helicase ortholog, Sgs1, plays central roles to coordinate the formation and resolution of joint molecule intermediates (JMs) during meiotic recombination in budding yeast. Sgs1 can associate with type-I topoisomerase Top3 and its accessory factor Rmi1 to form a conserved complex best known for its unique ability to decatenate double-Holliday junctions. Contrary to expectations, we show that the strand-passage activity of Top3-Rmi1 is required for all known functions of Sgs1 in meiotic recombination, including channeling JMs into physiological crossover and noncrossover pathways, and suppression of non-allelic recombination. We infer that Sgs1 always functions in the context of the Sgs1-Top3-Rmi1 complex to regulate meiotic recombination. In addition, we reveal a distinct late role for Top3-Rmi1 in resolving recombination-dependent chromosome entanglements to allow segregation at anaphase. Surprisingly, Sgs1 does not share this essential role of Top3-Rmi1. These data reveal an essential and pervasive role for the Top3-Rmi1 decatenase during meiosis.
布鲁姆解旋酶的直系同源物Sgs1,在芽殖酵母减数分裂重组过程中,对于协调联合分子中间体(JMs)的形成和分解起着核心作用。Sgs1可以与I型拓扑异构酶Top3及其辅助因子Rmi1结合,形成一种保守的复合物,该复合物以其独特的解开双Holliday连接的能力而闻名。与预期相反,我们发现Top3-Rmi1的链转移活性对于Sgs1在减数分裂重组中的所有已知功能都是必需的,包括将JMs引导到生理性交叉和非交叉途径,以及抑制非等位基因重组。我们推断Sgs1总是在Sgs1-Top3-Rmi1复合物的背景下起作用来调节减数分裂重组。此外,我们揭示了Top3-Rmi1在解决依赖重组的染色体缠结以允许后期分离方面有一个独特的后期作用。令人惊讶的是,Sgs1并不共享Top3-Rmi1的这一基本作用。这些数据揭示了Top3-Rmi1解连环酶在减数分裂过程中的一个基本且普遍的作用。