University of Hamburg, Department of Developmental Biology, Ohnhorststr. 18, D-22609 Hamburg, Germany.
Nucleic Acids Res. 2020 Nov 18;48(20):11521-11535. doi: 10.1093/nar/gkaa527.
HORMA domain-containing proteins (HORMADs) play an essential role in meiosis in many organisms. The meiotic HORMADs, including yeast Hop1, mouse HORMAD1 and HORMAD2, and Arabidopsis ASY1, assemble along chromosomes at early prophase and the closure motif at their C-termini has been hypothesized to be instrumental for this step by promoting HORMAD oligomerization. In late prophase, ASY1 and its homologs are progressively removed from synapsed chromosomes promoting chromosome synapsis and recombination. The conserved AAA+ ATPase PCH2/TRIP13 has been intensively studied for its role in removing HORMADs from synapsed chromosomes. In contrast, not much is known about how HORMADs are loaded onto chromosomes. Here, we reveal that the PCH2-mediated dissociation of the HORMA domain of ASY1 from its closure motif is important for the nuclear targeting and subsequent chromosomal loading of ASY1. This indicates that the promotion of ASY1 to an 'unlocked' state is a prerequisite for its nuclear localization and chromosomal assembly. Likewise, we find that the closure motif is also necessary for the removal of ASY1 by PCH2 later in prophase. Our work results in a unified new model for PCH2 and HORMADs function in meiosis and suggests a mechanism to contribute to unidirectionality in meiosis.
HORMA 结构域蛋白（HORMADs）在许多生物的减数分裂中发挥着重要作用。减数分裂中的 HORMADs，包括酵母 Hop1、小鼠 HORMAD1 和 HORMAD2 以及拟南芥 ASY1，在早期前中期沿染色体组装，其 C 末端的封闭基序被假设通过促进 HORMAD 寡聚化来促进这一步骤。在前中期晚期，ASY1 及其同源物逐渐从联会染色体上移除，从而促进染色体联会和重组。保守的 AAA+ATP 酶 PCH2/TRIP13 因其在从联会染色体上去除 HORMADs 方面的作用而受到广泛研究。相比之下，关于 HORMADs 如何加载到染色体上的信息知之甚少。在这里，我们揭示了 PCH2 介导的 ASY1 的 HORMA 结构域与其封闭基序的解离对于 ASY1 的核靶向和随后的染色体加载是重要的。这表明促进 ASY1 进入“解锁”状态是其核定位和染色体组装的前提条件。同样，我们发现封闭基序对于 PCH2 在前期后期去除 ASY1 也是必需的。我们的工作为 PCH2 和 HORMADs 在减数分裂中的功能提供了一个统一的新模型，并提出了一种有助于减数分裂单向性的机制。
