Aurora B-mediated localized delays in nuclear envelope formation facilitate inclusion of late-segregating chromosome fragments.
Aurora B-mediated localized delays in nuclear envelope formation facilitate inclusion of late-segregating chromosome fragments.
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DOI：
10.1091/mbc.e15-01-0026
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发表时间：
2015-06-15
影响因子：
3.3
通讯作者：
Sullivan W
中科院分区：
文献类型：
--
作者：
Karg T;Warecki B;Sullivan W
无着丝粒染色体在有丝分裂中表现出延迟分离。这些延迟是如何影响核膜重组的还不完全清楚。被Aurora B包被的落后无着丝粒在核膜中诱导高度局部化的间隙以允许无着丝粒进入子核。极光B减少后，间隙形成减少。为了确定染色体分离是如何与核膜形成（NEF）相协调的，我们研究了果蝇神经母细胞中存在落后无着丝粒染色体时NEF的动态。无着丝粒染色体通常表现出延迟但最终成功的分离和整合到子核中。然而，这是未知的，这些后期分离的无着丝粒片段是否影响NEF，以确保其包含在子核。通过现场分析，我们表明，无着丝粒染色体诱导高度本地化的延迟在核膜的重组。这些延迟导致核膜中的间隙，这有利于将滞后的无着丝粒体纳入末期子核。核膜重组的局部延迟需要极光B激酶活性。在Aurora B活性降低的细胞中，局部核膜重组延迟的频率降低，导致无中心的核纤层蛋白包被微核的频率增加。这些研究揭示了极光B在维持基因组的完整性，通过促进形成一个通道，在核膜中的晚期分离的无着丝粒染色体进入末期的子核的新的作用。
Acentric chromosomes exhibit delayed segregation during mitosis. How these delays affect nuclear envelope reassembly is not fully understood. Lagging acentrics coated with Aurora B induce a highly localized gap in the nuclear envelope to allow acentric entry into daughter nuclei. Gap formation is decreased upon reduction of Aurora B. To determine how chromosome segregation is coordinated with nuclear envelope formation (NEF), we examined the dynamics of NEF in the presence of lagging acentric chromosomes in Drosophila neuroblasts. Acentric chromosomes often exhibit delayed but ultimately successful segregation and incorporation into daughter nuclei. However, it is unknown whether these late-segregating acentric fragments influence NEF to ensure their inclusion in daughter nuclei. Through live analysis, we show that acentric chromosomes induce highly localized delays in the reassembly of the nuclear envelope. These delays result in a gap in the nuclear envelope that facilitates the inclusion of lagging acentrics into telophase daughter nuclei. Localized delays of nuclear envelope reassembly require Aurora B kinase activity. In cells with reduced Aurora B activity, there is a decrease in the frequency of local nuclear envelope reassembly delays, resulting in an increase in the frequency of acentric-bearing, lamin-coated micronuclei. These studies reveal a novel role of Aurora B in maintaining genomic integrity by promoting the formation of a passageway in the nuclear envelope through which late-segregating acentric chromosomes enter the telophase daughter nucleus.