Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208.
Mol Biol Cell. 2022 Dec 1;33(14):br25. doi: 10.1091/mbc.E22-07-0297. Epub 2022 Oct 12.
Although end-on microtubule-kinetochore attachments typically drive chromosome alignment, oocytes do not form these connections. Instead, microtubule bundles run laterally alongside chromosomes and a ring-shaped protein complex facilitates congression (the "ring complex", RC). Here, we report new aspects of RC and chromosome structure that are required for congression and segregation. First, we found that in addition to encircling the outside of each homologous chromosome pair (bivalent), the RC also forms internal subloops that wrap around the domains where cohesion is lost during the first meiotic division; cohesin removal could therefore disengage these subloops in anaphase, enabling RC removal from chromosomes. Additionally, we discovered new features of chromosome organization that facilitate congression. Analysis of a mutant that forms bivalents with a fragile, unresolved homolog interface revealed that these bivalents are usually able to biorient on the spindle, with lateral microtubule bundles running alongside them and constraining the chromosome arms so that the two homologs are pointed to opposite spindle poles. This biorientation facilitates congression, as monooriented bivalents exhibited reduced polar ejection forces that resulted in congression defects. Thus, despite not forming end-on attachments, chromosome biorientation promotes congression in oocytes. Our work therefore reveals novel features of chromosome organization in oocytes and highlights the importance of proper chromosome structure for faithful segregation during meiotic divisions.
尽管端对端微管-动粒连接通常驱动染色体的排列，但卵母细胞并不形成这些连接。相反，微管束沿染色体侧向运行，一个环形蛋白复合物促进着染色体的聚集（“环复合物”，RC）。在这里，我们报告了 RC 和染色体结构的新方面，这些方面对于聚集和分离是必需的。首先，我们发现，除了环绕每对同源染色体（二价体）的外部，RC 还形成内部的亚环，这些亚环围绕着在第一次减数分裂中丢失着丝粒的区域；因此，在后期，着丝粒的去除可以使这些亚环脱离，从而使 RC 从染色体上脱离。此外，我们发现了促进聚集的染色体组织的新特征。对一个形成脆弱、未解决的同源界面的二价体的突变体的分析表明，这些二价体通常能够在纺锤体上双定向，侧向微管束沿着它们运行，并约束染色体臂，使两个同源物指向相反的纺锤极。这种双定向促进了聚集，因为单定向的二价体表现出减少的极排斥力，导致聚集缺陷。因此，尽管卵母细胞不形成端对端的连接，但染色体的双定向促进了聚集。因此，我们的工作揭示了卵母细胞中染色体组织的新特征，并强调了适当的染色体结构对于减数分裂过程中忠实分离的重要性。
