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Cells enter a unique intermediate 4N stage, not 4N-G1, after aborted mitosis.

机译:在有丝分裂终止后,细胞进入独特的4N中间阶段,而不是4N-G1。

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摘要

It is widely accepted that mammalian cells enter the next G(1)-phase (G(1)) with 4N DNA after slippage from prolonged drug-induced mitotic block caused by activation of the transient spindle checkpoint. Understanding cell fate after mitotic slippage (MS) has significant clinical importance. The conclusion the MS cells enter 4N-G(1) is based on morphology and mitotic cyclin destruction. Definitive biochemical evidence for G(1) is scarce or unconvincing, in part because of methods of protein extraction required for immunoblot analysis that cannot take into account the cell cycle heterogeneity of cell cultures. We used single-cell-intracellular-flow-cytometric analysis to further define important factors determining cell fate after MS. Results from human and mouse embryonic stem cells (ESC) that reenter polyploid cell cycles are compared to human somatic cells that die after MS. We conclude that phosphorylation status of pRb, p53, CDK1, and especially cyclin B1 levels are important for cell fate decision in MS cells, which occur in a unique, intervening, non-G(1), tetraploid subphase.
机译:广泛接受的是哺乳动物细胞从暂时性纺锤体检查点的激活导致的药物诱导的有丝分裂阻滞延长而滑落后,进入具有4N DNA的下一个G(1)期(G(1))。了解有丝分裂滑移(MS)后的细胞命运具有重要的临床意义。 MS细胞进入4N-G(1)的结论是基于形态学和有丝分裂细胞周期蛋白的破坏。 G(1)的确切生化证据很少或令人信服,部分原因是免疫印迹分析所需的蛋白质提取方法无法考虑细胞培养物的细胞周期异质性。我们使用单细胞细胞内流式细胞仪分析来进一步定义重要因素,确定MS后细胞命运。将进入多倍体细胞周期的人和小鼠胚胎干细胞(ESC)的结果与MS后死亡的人体细胞进行比较。我们得出结论,pRb,p53,CDK1,尤其是细胞周期蛋白B1的磷酸化状态对于MS细胞的细胞命运决定很重要,MS细胞发生在唯一的,中间的非G(1)四倍体亚相中。

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