蛋白磷酸酶4在Hop1组装中的减数分裂DNA双链断裂独立作用促进芽殖酵母减数分裂染色体轴形成,Genes to Cells

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蛋白磷酸酶4在Hop1组装中的减数分裂DNA双链断裂独立作用促进芽殖酵母减数分裂染色体轴形成
Genes to Cells ( IF 1.3 ) Pub Date : 2023-05-27 , DOI: 10.1111/gtc.13049
Ke Li _{1,

2,

3} , Kei Yoshimura ₃ , Miki Shinohara _{1,

3,

4}

Affiliation

减数分裂前期发生的染色体结构的动态变化在减数分裂的进展中起着重要作用。其中，减数分裂特异性染色体轴环结构作为减数分裂重组反应和相关检查点系统之间集成控制的支架非常重要，以确保准确的染色体分离。然而，染色体轴环构建初始步骤的分子机制尚不清楚。在这里，我们发现，在芽殖酵母中，主要抵消 Mec1/Tel1 磷酸化的蛋白磷酸酶 4 (PP4) 是通过与 Hop1 相互作用促进染色体轴成分 Hop1 和 Red1 组装到减数分裂染色质上所必需的。另一方面，PP4 对 Rec8 汇编的影响较小。值得注意的是，与之前已知的 PP4 功能不同，Hop1/Red1 组装中的 PP4 功能独立于减数分裂 DSB 依赖性 Tel1/Mec1 激酶活性。在缺乏 PP4 功能的情况下，Hop1/Red1 组装的缺陷不会被 Pch2 的功能障碍所抑制，Pch2 会从染色体轴上去除 Hop1 蛋白，这表明 PP4 是 Hop1 染色质加载的初始步骤所必需的，而不是 Hop1 的稳定作用。轴。这些结果表明，在减数分裂双链断裂形成之前的染色体轴构建过程中，磷酸化/去磷酸化介导的 Hop1 募集到染色质上的调节。

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Meiotic DNA double-strand break-independent role of protein phosphatase 4 in Hop1 assembly to promote meiotic chromosome axis formation in budding yeast

Dynamic changes in chromosomal structure that occur during meiotic prophase play an important role in the progression of meiosis. Among them, meiosis-specific chromosomal axis-loop structures are important as a scaffold for integrated control between the meiotic recombination reaction and the associated checkpoint system to ensure accurate chromosome segregation. However, the molecular mechanism of the initial step of chromosome axis-loop construction is not well understood. Here, we showed that, in budding yeast, protein phosphatase 4 (PP4) that primarily counteracts Mec1/Tel1 phosphorylation is required to promote the assembly of a chromosomal axis component Hop1 and Red1 onto meiotic chromatin via interaction with Hop1. PP4, on the other hand, less affects Rec8 assembly. Notably, unlike the previously known function of PP4, this PP4 function in Hop1/Red1 assembly was independent of meiotic DSB-dependent Tel1/Mec1 kinase activities. The defect in Hop1/Red1 assembly in the absence of PP4 function was not suppressed by dysfunction of Pch2, which removes Hop1 protein from the chromosome axis, suggesting that PP4 is required for the initial step of chromatin loading of Hop1 rather than stabilization of Hop1 on axes. These results indicate phosphorylation/dephosphorylation-mediated regulation of Hop1 recruitment onto chromatin during chromosome axis construction before meiotic double-strand break formation.

更新日期：2023-05-27

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