Department of Molecular and Cellular Biology, University of California, Davis, Davis, CA 95616, USA.
Genetics. 2022 May 5;221(1). doi: 10.1093/genetics/iyac045.
During meiosis, chromosomes undergo dramatic changes in structural organization, nuclear positioning, and motion. Although the nuclear pore complex has been shown to affect genome organization and function in vegetative cells, its role in meiotic chromosome dynamics has remained largely unexplored. Recent work in the budding yeast Saccharomyces cerevisiae demonstrated that the mobile nucleoporin Nup2 is required for normal progression through meiosis I prophase and sporulation in strains where telomere-led chromosome movement has been compromised. The meiotic-autonomous region, a short fragment of Nup2 responsible for its role in meiosis, was shown to localize to the nuclear envelope via Nup60 and to bind to meiotic chromosomes. To understand the relative contribution these 2 activities have on meiotic-autonomous region function, we first carried out a screen for meiotic-autonomous region mutants defective in sporulation and found that all the mutations disrupt interaction with both Nup60 and meiotic chromosomes. Moreover, nup60 mutants phenocopy nup2 mutants, exhibiting similar nuclear division kinetics, sporulation efficiencies, and genetic interactions with mutations that affect the telomere bouquet. Although full-length Nup60 requires Nup2 for function, removal of Nup60's C-terminus allows Nup60 to bind meiotic chromosomes and promotes sporulation without Nup2. In contrast, binding of the meiotic-autonomous region to meiotic chromosomes is completely dependent on Nup60. Our findings uncover an inhibitory function for the Nup60 C-terminus and suggest that Nup60 mediates recruitment of meiotic chromosomes to the nuclear envelope, while Nup2 plays a secondary role counteracting the inhibitory function in Nup60's C-terminus.
在减数分裂过程中,染色体的结构组织、核定位和运动发生了显著变化。尽管核孔复合物已被证明会影响营养细胞的基因组组织和功能,但它在减数分裂染色体动力学中的作用在很大程度上仍未得到探索。最近在芽殖酵母酿酒酵母中的研究表明,可移动核孔蛋白 Nup2 是正常通过减数分裂 I 前期和在端粒引导的染色体运动受损的菌株中进行孢子形成所必需的。被证明通过 Nup60 定位于核膜并与减数分裂染色体结合的 Nup2 的短片段减数自主区,负责其在减数分裂中的作用。为了了解这 2 种活性对减数自主区功能的相对贡献,我们首先进行了减数自主区突变体在孢子形成中的缺陷筛选,发现所有突变都破坏了与 Nup60 和减数分裂染色体的相互作用。此外,nup60 突变体模拟了 nup2 突变体,表现出类似的核分裂动力学、孢子形成效率以及与影响端粒花束的突变的遗传相互作用。尽管全长 Nup60 需要 Nup2 才能发挥功能,但去除 Nup60 的 C 末端允许 Nup60 结合减数分裂染色体,并在没有 Nup2 的情况下促进孢子形成。相比之下,减数自主区与减数分裂染色体的结合完全依赖于 Nup60。我们的发现揭示了 Nup60 C 末端的抑制功能,并表明 Nup60 介导将减数分裂染色体募集到核膜,而 Nup2 发挥次要作用,抵消 Nup60 C 末端的抑制功能。