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有丝分裂纺锤体几何形状的瞬时缺陷和染色体分离错误。

Transient defects of mitotic spindle geometry and chromosome segregation errors.

机构信息

Department of Biological Sciences, Virginia Tech, 1981 Kraft Dr, Blacksburg, VA, 24061, USA.

出版信息

Cell Div. 2012 Aug 11;7(1):19. doi: 10.1186/1747-1028-7-19.

Abstract

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.

摘要

双极有丝分裂纺锤体的组装对于确保染色体分离的准确性和防止非整倍体至关重要,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,从而使细胞能够用双极纺锤体完成有丝分裂,并进行双极染色体分离,从而防止与异常纺锤体结构相关的细胞死亡风险。尽管这似乎是一种有利的策略,但纺锤体几何形状的短暂缺陷对细胞群体或生物体的威胁可能比永久性纺锤体缺陷更大。事实上,暂时的纺锤体几何缺陷会导致高比例的染色体错误分离和非整倍体。在这篇综述中,我们总结了我们目前对两种特定类型的瞬时纺锤体几何缺陷(瞬时多极性和不完全纺锤体极分离)的了解,并描述了这些机制如何导致染色体错误分离和非整倍体。最后,我们讨论了这些瞬时纺锤体缺陷如何特异性地导致癌细胞中观察到的染色体不稳定性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/68e5/3509025/1b64030931ad/1747-1028-7-19-1.jpg

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