Faculty of Life Sciences, University of Manchester, MIB, 131 Princess Street, Manchester, M1 7DN, UK.
Chromosome Res. 2010 Jul;18(5):525-41. doi: 10.1007/s10577-010-9137-8. Epub 2010 Jun 22.
Cell type and tissue architecture correlate with genome organization in higher eukaryotes, and structural nuclear landmarks are faithfully transmitted from one cell generation to the next. However, how nuclear components find their place in the nucleus after mitosis is still a matter of debate. As the major structural proteins within nuclei, the nuclear lamins are good candidates to re-establish nuclear compartments following mitosis. Human cells with reduced expression of the major B-type lamin protein, lamin B1, were generated using RNA interference. Mitotic and nuclear assembly phenotypes were then visualized in both fixed and living cells. Mitotic defects in lamin B1-depleted cells correlated with a general deterioration in nuclear compartmentalization and chromatin structure, frequent failure of chromosome segregation, and profound disorganization of centromeres. Examination of cells with normal lamin B1 expression indicated that small lamin B1 foci remain associated with major nuclear compartments--chromatin, nucleoli, and nuclear speckles--during an unperturbed mitosis. Our experiments show that normal lamin B1 expression is required for successful cell division and provide preliminary evidence that lamin B1-containing remnants of the interphase nucleoskeleton persist throughout mitosis. We suggest that these residual structures provide landmarks that are targeted during nuclear reassembly to allow key features of nuclear organization to be inherited from one cell cycle to the next.
在高等真核生物中，细胞类型和组织架构与基因组组织相关，结构核标志物在下一个细胞世代中被准确传递。然而，核成分在有丝分裂后如何在核内找到自己的位置仍然存在争议。作为核内的主要结构蛋白，核纤层蛋白是在有丝分裂后重新建立核区室的良好候选物。使用 RNA 干扰技术生成了表达主要 B 型核纤层蛋白 lamin B1 减少的人类细胞。然后在固定和活细胞中观察有丝分裂和核组装表型。lamin B1 耗竭细胞中的有丝分裂缺陷与核区室化和染色质结构的普遍恶化、染色体分离的频繁失败以及着丝粒的严重紊乱相关。对 lamin B1 表达正常的细胞的检查表明，在未受干扰的有丝分裂过程中，小的 lamin B1 焦点仍然与主要核区室——染色质、核仁、核斑点相关联。我们的实验表明，正常的 lamin B1 表达是细胞分裂成功所必需的，并提供了初步证据，证明 lamin B1 包含的核间骨架残留物在整个有丝分裂过程中持续存在。我们认为，这些残余结构提供了地标，在核重排过程中被靶向，以便将核组织的关键特征从一个细胞周期传递到下一个细胞周期。
