Department of Chemistry and Molecular Biology, University of Gothenburg, Gothenburg, Sweden.
Life Sciences Institute, Zhejiang University, Hangzhou, China.
Sci Adv. 2019 Jan 23;5(1):eaau9780. doi: 10.1126/sciadv.aau9780. eCollection 2019 Jan.
Segregation of homologous chromosomes in meiosis I is tightly regulated by their physical links, or crossovers (COs), generated from DNA double-strand breaks (DSBs) through meiotic homologous recombination. In budding yeast, three ZMM (Zip1/2/3/4, Mer3, Msh4/5) proteins, Zip2, Zip4, and Spo16, form a "ZZS" complex, functioning to promote meiotic recombination via a DSB repair pathway. Here, we identified the mammalian ortholog of Spo16, termed SPO16, which interacts with the mammalian ortholog of Zip2 (SHOC1/MZIP2), and whose functions are evolutionarily conserved to promote the formation of COs. SPO16 localizes to the recombination nodules, as SHOC1 and TEX11 do. SPO16 is required for stabilization of SHOC1 and proper localization of other ZMM proteins. The DSBs formed in SPO16-deleted meiocytes were repaired without COs formation, although synapsis is less affected. Therefore, formation of SPO16-SHOC1 complex-associated recombination intermediates is a key step facilitating meiotic recombination that produces COs from yeast to mammals.
减数分裂 I 中同源染色体的分离受到其物理连接（或交叉）的严格调控，这些连接是通过减数分裂同源重组从 DNA 双链断裂（DSB）产生的。在 budding yeast 中，三个 ZMM（Zip1/2/3/4、Mer3、Msh4/5）蛋白，Zip2、Zip4 和 Spo16，形成了一个“ZZS”复合物，通过 DSB 修复途径促进减数分裂重组。在这里，我们鉴定了 Spo16 的哺乳动物同源物，称为 SPO16，它与哺乳动物的 Zip2 同源物（SHOC1/MZIP2）相互作用，其功能在进化上是保守的，以促进 CO 的形成。SPO16 定位于重组结节，就像 SHOC1 和 TEX11 一样。SPO16 对于 SHOC1 的稳定和其他 ZMM 蛋白的正确定位是必需的。在 SPO16 缺失的减数分裂细胞中形成的 DSB 没有 CO 形成，但联会的影响较小。因此，形成 SPO16-SHOC1 复合物相关的重组中间体是一个关键步骤，促进了从酵母到哺乳动物的减数分裂重组产生 CO。
