Mitotic catastrophe occurs in the absence of apoptosis in p53-null cells with a defective G1 checkpoint.
Mitotic catastrophe occurs in the absence of apoptosis in p53-null cells with a defective G1 checkpoint.
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DOI：
10.1371/journal.pone.0022946
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Beard P
中科院分区：
文献类型：
--
作者：
Fragkos M;Beard P
有丝分裂过程中发生的细胞死亡或有丝分裂灾难通常与细胞凋亡同时发生，但有丝分裂灾难可能表现出程序性细胞死亡特征的条件仍不清楚。在这里介绍的工作中，我们研究了有丝分裂细胞死亡，利用紫外线灭活的细小病毒（腺相关病毒; AAV），已被证明诱导DNA损伤反应和随后的死亡的p53缺陷细胞在有丝分裂，而不影响宿主基因组的完整性。缺乏p53和缺乏G1细胞周期检查点的骨肉瘤细胞（U2 OSp 53 DD）通过短暂的G2停滞对AAV感染作出反应。我们发现感染的U2 OSp 53 DD细胞通过有丝分裂灾难死亡，没有染色体凝聚或DNA片段化的迹象。此外，细胞死亡是独立的半胱天冬酶，凋亡诱导因子（AIF），自噬和坏死性凋亡。这些发现证实了AAV感染后的细胞形态的延时显微镜。所使用的分析很容易揭示其他细胞类型的凋亡时，它确实发生。两者合计的结果表明，在G1检查点的情况下，有丝分裂灾难发生在这些p53无效的细胞主要是由于机械破坏诱导的中心体过度复制，而不是作为自杀信号的后果。
Cell death occurring during mitosis, or mitotic catastrophe, often takes place in conjunction with apoptosis, but the conditions in which mitotic catastrophe may exhibit features of programmed cell death are still unclear. In the work presented here, we studied mitotic cell death by making use of a UV-inactivated parvovirus (adeno-associated virus; AAV) that has been shown to induce a DNA damage response and subsequent death of p53-defective cells in mitosis, without affecting the integrity of the host genome. Osteosarcoma cells (U2OSp53DD) that are deficient in p53 and lack the G1 cell cycle checkpoint respond to AAV infection through a transient G2 arrest. We found that the infected U2OSp53DD cells died through mitotic catastrophe with no signs of chromosome condensation or DNA fragmentation. Moreover, cell death was independent of caspases, apoptosis-inducing factor (AIF), autophagy and necroptosis. These findings were confirmed by time-lapse microscopy of cellular morphology following AAV infection. The assays used readily revealed apoptosis in other cell types when it was indeed occurring. Taken together the results indicate that in the absence of the G1 checkpoint, mitotic catastrophe occurs in these p53-null cells predominantly as a result of mechanical disruption induced by centrosome overduplication, and not as a consequence of a suicide signal.
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DOI：
10.1038/nrm2718
发表时间：
2009-07
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.3
作者：
Fragkos, Michalis;Jurvansuu, Jaana;Beard, Peter
通讯作者：
Beard, Peter
影响因子：
5.4
作者：
Fragkos, Michalis;Breuleux, Madlaina;Beard, Peter
通讯作者：
Beard, Peter
影响因子：
3.4
作者：
Cromheecke, M;Piers, BA;Hoekstra, HJ
通讯作者：
Hoekstra, HJ
影响因子：
11.4
作者：
Dodson, H;Bourke, E;Morrison, C
通讯作者：
Morrison, C