Laboratory of Cell and Molecular Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Curr Biol. 2012 Jun 19;22(12):1128-33. doi: 10.1016/j.cub.2012.04.022. Epub 2012 May 31.
The mechanisms that dictate nuclear shape are largely unknown. Here we screened the budding yeast deletion collection for mutants with abnormal nuclear shape. A common phenotype was the appearance of a nuclear extension, particularly in mutants in DNA repair and chromosome segregation genes. Our data suggest that these mutations led to the abnormal nuclear morphology indirectly, by causing a checkpoint-induced cell-cycle delay. Indeed, delaying cells in mitosis by other means also led to the appearance of nuclear extensions, whereas inactivating the DNA damage checkpoint pathway in a DNA repair mutant reduced the fraction of cells with nuclear extensions. Formation of a nuclear extension was specific to a mitotic delay, because cells arrested in S or G2 had round nuclei. Moreover, the nuclear extension always coincided with the nucleolus, while the morphology of the DNA mass remained largely unchanged. Finally, we found that phospholipid synthesis continued unperturbed when cells delayed in mitosis, and inhibiting phospholipid synthesis abolished the formation of nuclear extensions. Our data suggest a mechanism that promotes nuclear envelope expansion during mitosis. When mitotic progression is delayed, cells sequester the added membrane to the nuclear envelope associated with the nucleolus, possibly to avoid disruption of intranuclear organization.
决定核形状的机制在很大程度上是未知的。在这里，我们筛选出芽殖酵母缺失库中具有异常核形状的突变体。一个常见的表型是核延伸的出现，特别是在 DNA 修复和染色体分离基因的突变体中。我们的数据表明，这些突变通过引起检查点诱导的细胞周期延迟，间接地导致了异常的核形态。事实上，通过其他手段延迟有丝分裂中的细胞也会导致核延伸的出现，而在 DNA 修复突变体中失活 DNA 损伤检查点途径会减少具有核延伸的细胞分数。核延伸的形成是有丝分裂延迟所特有的，因为处于 S 期或 G2 期的细胞具有圆形核。此外，核延伸总是与核仁一致，而 DNA 质的形态基本保持不变。最后，我们发现当细胞在有丝分裂中延迟时，磷脂合成继续不受干扰，而抑制磷脂合成则会破坏核延伸的形成。我们的数据提出了一种在有丝分裂期间促进核膜扩展的机制。当有丝分裂进程延迟时，细胞将额外的膜隔离到与核仁相关的核膜上，可能是为了避免核内组织的破坏。
