Vicars Hannah, Mills Alison, Karg Travis, Sullivan William
Department of Molecular, Cell and Developmental Biology, University of California, 1156 High Street Santa Cruz, Santa Cruz, CA 95064, USA.
Genetics. 2025 Feb 5;229(2). doi: 10.1093/genetics/iyae188.
Chromosome congression and alignment on the metaphase plate involves lateral and microtubule plus-end interactions with the kinetochore. Here we take advantage of our ability to efficiently generate a GFP-marked acentric X chromosome fragment in Drosophila neuroblasts to identify forces acting on chromosome arms that drive congression and alignment. We find acentrics efficiently congress and align on the metaphase plate, often more rapidly than kinetochore-bearing chromosomes. Unlike intact chromosomes, the paired sister acentrics oscillate as they move to and reside on the metaphase plate in a plane distinct and significantly further from the main mass of intact chromosomes. Consequently, at anaphase onset, acentrics are oriented either parallel or perpendicular to the spindle. Parallel-oriented sisters separate by sliding while those oriented perpendicularly separate via unzipping. This oscillation, together with the fact that in the presence of spindles with disrupted interpolar microtubules acentrics are rapidly shunted away from the poles, indicates that distributed plus-end-directed forces are primarily responsible for acentric migration. This conclusion is supported by the observation that reduction of EB1 preferentially disrupts acentric alignment. Taken together, these studies suggest that plus-end forces mediated by the outer interpolar microtubules contribute significantly to acentric congression and alignment. Surprisingly, we observe disrupted telomere pairing and alignment of sister acentrics indicating that the kinetochore is required to ensure proper gene-to-gene alignment of sister chromatids. Finally, we demonstrate that like mammalian cells, the Drosophila congressed chromosomes on occasion exhibit a toroid configuration.
染色体在中期板上的汇聚和排列涉及到与动粒的侧向和微管正端相互作用。在这里,我们利用在果蝇神经母细胞中高效生成绿色荧光蛋白标记的无着丝粒X染色体片段的能力,来识别作用于染色体臂上驱动汇聚和排列的力。我们发现无着丝粒染色体能有效地在中期板上汇聚和排列,其速度通常比带有着丝粒的染色体更快。与完整染色体不同,配对的无着丝粒姐妹染色单体在移向并停留在中期板上时会振荡,它们所在的平面与完整染色体的主体平面不同,且距离更远。因此,在后期开始时,无着丝粒染色体与纺锤体平行或垂直排列。平行排列的姐妹染色单体通过滑动分开,而垂直排列的则通过拉开分开。这种振荡,以及在极间微管被破坏的纺锤体存在时无着丝粒染色体迅速被从两极推开这一事实,表明分布的正端定向力是无着丝粒染色体迁移的主要原因。EB1减少优先破坏无着丝粒染色体排列的观察结果支持了这一结论。综上所述,这些研究表明,由极间微管介导的正端力对无着丝粒染色体的汇聚和排列有显著贡献。令人惊讶的是,我们观察到姐妹无着丝粒染色体的端粒配对和排列被破坏,这表明需要动粒来确保姐妹染色单体基因间的正确排列。最后,我们证明,与哺乳动物细胞一样,果蝇中汇聚的染色体有时会呈现环形结构。