Mammalian cells lack checkpoints for tetraploidy, aberrant centrosome number, and cytokinesis failure

被引:112
作者
Wong, C
Stearns, T [1 ]
机构
[1] Stanford Univ, Dept Biol Sci, Stanford, CA 94305 USA
[2] Stanford Univ, Sch Med, Dept Genet, Stanford, CA 94305 USA
关键词
D O I
10.1186/1471-2121-6-6
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Background: Mammalian cells have been reported to have a p53-dependent tetraploidy checkpoint that blocks cell cycle progression in GI in response to failure of cell division. In most cases where the tetraploidy checkpoint has been observed cell division was perturbed by anti-cytoskeleton drug treatments. However, other evidence argues against the existence of a tetraploidy checkpoint. Cells that have failed to divide differ from normal cells in having two nuclei, two centrosomes, a decreased surface to volume ratio, and having undergone an abortive cytokinesis. We tested each of these to determine which, if any, cause a GI cell cycle arrest. Results: Primary human diploid fibroblasts with intact cell cycle checkpoints were used in all experiments. Synchronized cells exhibited GI arrest in response to division failure caused by treatment with either cytochalasin or the myosin II inhibitor blebbistatin. The role of tetraploidy, aberrant centrosome number, and increased cell size were tested by cell/cell and cell/cytoplast fusion experiments; none of these conditions resulted in GI arrest. Instead we found that various drug treatments of the cells resulted in cellular damage, which was the likely cause of the arrest. When cytokinesis was blocked in the absence of damage-inducing drug treatments no GI arrest was observed. Conclusions: We show that neither tetraploidy, aberrant centrosome number, cell size, nor failure of cytokinesis lead to GI arrest, suggesting that there is no tetraploidy checkpoint. Rather, certain standard synchronization treatments cause damage that is the likely cause of GI arrest. Since tetraploid cells can cycle when created with minimal manipulation, previous reports of a tetraploidy checkpoint can probably be explained by side effects of the drug treatments used to observe them.
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页数:12
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