COMET Functions as a PCH2 Cofactor in Regulating the HORMA Domain Protein ASY1
COMET Functions as a PCH2 Cofactor in Regulating the HORMA Domain Protein ASY1
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DOI：
10.1016/j.cub.2020.07.089
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发表时间：
2020-11-02
期刊：
影响因子：
9.2
通讯作者：
Schnittger, Arp
中科院分区：
文献类型：
--
作者：
Balboni, Martina;Yang, Chao;Schnittger, Arp
染色体轴的形成是减数分裂重组的关键，因此也是染色体正确分配到减数分裂产物的关键。拟南芥中轴的一个关键组成部分是 HORMA 结构域蛋白 (HORMAD) ASY1，它是酵母中 Hop1 和哺乳动物中 HORMAD1/2 的同源物。 ASY1 的染色体关联是动态的，即 ASY1 在早期早期被招募到轴上，随后在同源染色体突触时大部分被移除。 PCH2/TRIP13 蛋白是众所周知的减数分裂 HORMAD 调节因子，并且是从突触染色体中耗尽它们所必需的。然而，在除芽殖酵母之外的任何生物体中，尚未发现 PCH2/TRIP13 与假定的 HORMAD 底物之间存在直接相互作用。因此，ASY1 和其他减数分裂 HORMAD 的动态如何控制仍然很大程度上难以捉摸。在这里，我们鉴定了 COMET，人类 p31(comet) 的拟南芥同源物，以其在纺锤体组装检查点 (SAC) 中的功能而闻名，是减数分裂中 ASY1 动力学的中央调节器。我们提供的证据表明 COMET 通过充当 PCH2 的适配器来控制 ASY1 本地化。由于 ASY1 在早期早期积累在细胞质中，并持续存在于彗星的染色体上，因此我们得出结论，COMET 对于将 ASY1 招募到细胞核以及随后从轴上去除都是必需的。这里揭示的 COMET 作为 PCH2 接头的功能与酵母和动物 SAC 中另一种 HORMAD Mad2 的调节非常相似，揭示了含有 HORMA 结构域的蛋白质复合物的保守调节模块。
The formation of the chromosome axis is key to meiotic recombination and hence the correct distribution of chromosomes to meiotic products. A key component of the axis in Arabidopsis is the HORMA domain protein (HORMAD) ASY1, the homolog of Hop1 in yeast andHORMAD1/2 in mammals. The chromosomal association of ASY1 is dynamic, i.e., ASY1 is recruited to the axis at early prophase and later largely removed when homologous chromosomes synapse. PCH2/TRIP13 proteins are well-known regulators of meiotic HORMADs and required for their depletion from synapsed chromosomes. However, no direct interaction has been found between PCH2/TRIP13 and the presumptive HORMAD substrates in any organism other than in budding yeast. Thus, it remains largely elusive how the dynamics of ASY1 and other meiotic HORMADs are controlled. Here, we have identified COMET, the Arabidopsis homolog of human p31(comet), which is known for its function in the spindle assembly checkpoint (SAC), as a central regulator of ASY1 dynamics in meiosis. We provide evidence that COMET controls ASY1 localization by serving as an adaptor for PCH2. Because ASY1 accumulates in the cytoplasm in early prophase and is persistently present on chromosomes in comet, we conclude that COMET is required for both the recruitment of ASY1 to the nucleus and the subsequent removal from the axis. The here-revealed function of COMET as an adaptor for PCH2 remarkably resembles the regulation of another HORMAD, Mad2, in the SAC in yeast and animals, revealing a conserved regulatory module of HORMA-domain-containing protein complexes.