The spindle assembly checkpoint (SAC) joins the machinery of chromosome-to-spindle microtubule attachment with that of the cell cycle to prevent missegregation of chromosomes during mitosis. Although a functioning SAC has been verified in a limited number of organisms, it is regarded as an evolutionarily conserved safeguard mechanism. In this report, we focus on the existence of the SAC in a single-celled parasitic eukaryote, Giardia intestinalis. Giardia belongs to Excavata, a large and diverse supergroup of unicellular eukaryotes in which SAC control has been nearly unexplored. We show that Giardia cells with absent or defective mitotic spindles due to the inhibitory effects of microtubule poisons do not arrest in mitosis; instead, they divide without any delay, enter the subsequent cell cycle and even reduplicate DNA before dying. We identified a limited repertoire of kinetochore and SAC components in the Giardia genome, indicating that this parasite is ill equipped to halt mitosis before the onset of anaphase via SAC control of chromosome-spindle microtubule attachment. Finally, based on overexpression, we show that Giardia Mad2, a core SAC protein in other eukaryotes, localizes along intracytoplasmic portions of caudal flagellar axonemes, but never within nuclei, even in mitotic cells with blocked spindles, where the SAC should be active. These findings are consistent with the absence of a conventional SAC, known from yeast and metazoans, in the parasitic protist Giardia.

中文翻译：

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双核单细胞寄生虫贾第鞭毛虫肠道中没有常规纺锤体有丝分裂检查点。

纺锤体装配检查点（SAC）将染色体到纺锤体微管的附着机制与细胞周期的机制结合在一起，以防止有丝分裂期间染色体的偏析。尽管已经在有限数量的生物体中验证了功能正常的SAC，但它被认为是进化上保守的保障机制。在本报告中，我们重点研究单细胞寄生真核生物贾第鞭毛虫中SAC的存在。贾第鞭毛虫属于Excavata，Excavata是一个庞大而多样的单细胞真核生物超群，其中对SAC的控制几乎未曾探索过。我们显示出由于微管毒物的抑制作用而缺少或有缺陷的有丝分裂纺锤体的贾第鞭毛虫细胞不会在有丝分裂中停滞。相反，它们分裂而没有任何延迟，进入随后的细胞周期，甚至在死亡前重新复制DNA。我们确定了贾第鞭毛虫基因组中的线粒体和SAC组件的库，表明该寄生虫在后期通过染色体纺锤体微管附着的SAC控制之前无法阻止有丝分裂。最后，基于过度表达，我们显示了其他真核生物中的核心SAC蛋白Giardia Mad2沿尾鞭毛轴突的胞质内定位，但从未在核内定位，即使在纺锤体受阻的有丝分裂细胞中也应处于SAC活跃的位置。这些发现与寄生原生动物贾第虫中缺乏从酵母和后生动物中已知的常规SAC一致。这表明该寄生虫在后期开始时通过染色体纺锤体微管附着的SAC控制无法阻止有丝分裂。最后，基于过度表达，我们显示了其他真核生物中的核心SAC蛋白Giardia Mad2沿着尾鞭毛轴突的胞浆内部分定位，但从未在核内定位，即使在纺锤体受阻的有丝分裂细胞中也应处于SAC活跃的位置。这些发现与寄生原生动物贾第虫中缺乏从酵母和后生动物中已知的常规SAC一致。这表明该寄生虫在后期开始时通过染色体纺锤体微管附着的SAC控制无法阻止有丝分裂。最后，基于过度表达，我们显示了其他真核生物中的核心SAC蛋白Giardia Mad2沿尾鞭毛轴突的胞质内定位，但从未在核内定位，即使在纺锤体受阻的有丝分裂细胞中也应处于SAC活跃的位置。这些发现与寄生原生动物贾第鞭毛虫中缺乏从酵母和后生动物中已知的常规SAC一致。SAC应该处于活动状态。这些发现与寄生原生动物贾第虫中缺乏从酵母和后生动物中已知的常规SAC一致。SAC应该处于活动状态。这些发现与寄生原生动物贾第虫中缺乏从酵母和后生动物中已知的常规SAC一致。