Karg Travis, Warecki Brandt, Sullivan William
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064.
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, Santa Cruz, CA 95064
Mol Biol Cell. 2015 Jun 15;26(12):2227-41. doi: 10.1091/mbc.E15-01-0026. Epub 2015 Apr 15.
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.
为了确定染色体分离是如何与核膜形成(NEF)协调的,我们在果蝇神经母细胞中存在落后无着丝粒染色体的情况下,研究了核膜形成的动力学。无着丝粒染色体通常表现出延迟但最终成功的分离并并入子核。然而,这些后期分离的无着丝粒片段是否会影响核膜形成以确保它们被纳入子核尚不清楚。通过实时分析,我们发现无着丝粒染色体在核膜重新组装过程中诱导高度局部化的延迟。这些延迟导致核膜出现间隙,便于落后的无着丝粒染色体纳入末期子核。核膜重新组装的局部延迟需要极光B激酶活性。在极光B活性降低的细胞中,局部核膜重新组装延迟的频率降低,导致携带无着丝粒的、有核纤层蛋白包被的微核频率增加。这些研究揭示了极光B在通过促进核膜中通道的形成来维持基因组完整性方面的新作用,后期分离的无着丝粒染色体通过该通道进入末期子核。