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Transient defects of mitotic spindle geometry and chromosome segregation errors

机译:有丝分裂纺锤体几何结构的瞬时缺陷和染色体分离错误

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摘要

Assembly of a bipolar mitotic spindle is essential to ensure accurate chromosome segregation and prevent aneuploidy, and severe mitotic spindle defects are typically associated with cell death. Recent studies have shown that mitotic spindles with initial geometric defects can undergo specific rearrangements so the cell can complete mitosis with a bipolar spindle and undergo bipolar chromosome segregation, thus preventing the risk of cell death associated with abnormal spindle structure. Although this may appear as an advantageous strategy, transient defects in spindle geometry may be even more threatening to a cell population or organism than permanent spindle defects. Indeed, transient spindle geometry defects cause high rates of chromosome mis-segregation and aneuploidy. In this review, we summarize our current knowledge on two specific types of transient spindle geometry defects (transient multipolarity and incomplete spindle pole separation) and describe how these mechanisms cause chromosome mis-segregation and aneuploidy. Finally, we discuss how these transient spindle defects may specifically contribute to the chromosomal instability observed in cancer cells.
机译:双极有丝分裂纺锤体的组装对于确保准确的染色体分离和防止非整倍性至关重要,而且严重的有丝分裂纺锤体缺陷通常与细胞死亡有关。最近的研究表明,具有初始几何缺陷的有丝分裂纺锤体可以进行特定的重排,因此细胞可以通过双极纺锤体完成有丝分裂并经历双极染色体分离,从而防止了因纺锤体结构异常而导致细胞死亡的风险。尽管这可能是一种有利的策略,但主轴几何形状中的瞬时缺陷可能比永久性主轴缺陷对细胞群体或生物的威胁更大。确实,短暂的纺锤几何形状缺陷会导致较高的染色体误分离和非整倍性。在这篇综述中,我们总结了关于两种特定类型的瞬时纺锤几何缺陷(瞬时多极性和不完全的纺锤极分离)的当前知识,并描述了这些机制如何导致染色体错分离和非整倍性。最后,我们讨论了这些短暂的纺锤体缺陷如何专门导致癌细胞中观察到的染色体不稳定性。

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