Department of Molecular Genetics, Ohio State University, Columbus, OH, USA.
EMBO J. 2011 Jun 3;30(13):2648-61. doi: 10.1038/emboj.2011.176.
The spindle assembly checkpoint (SAC) arrests mitosis until bipolar attachment of spindle microtubules to all chromosomes is accomplished. However, when spindle formation is prevented and the SAC cannot be satisfied, mammalian cells can eventually overcome the mitotic arrest while the checkpoint is still activated. We find that Aspergillus nidulans cells, which are unable to satisfy the SAC, inactivate the checkpoint after a defined period of mitotic arrest. Such SAC inactivation allows normal nuclear reassembly and mitotic exit without DNA segregation. We demonstrate that the mechanisms, which govern such SAC inactivation, require protein synthesis and can occur independently of inactivation of the major mitotic regulator Cdk1/Cyclin B or mitotic exit. Moreover, in the continued absence of spindle function cells transit multiple cell cycles in which the SAC is reactivated each mitosis before again being inactivated. Such cyclic activation and inactivation of the SAC suggests that it is subject to cell-cycle regulation that is independent of bipolar spindle function.
纺锤体装配检查点（SAC）会阻止有丝分裂，直到纺锤体微管与所有染色体的双极附着完成。然而，当纺锤体的形成受到阻碍，SAC 无法得到满足时，哺乳动物细胞最终可以在检查点仍然被激活的情况下克服有丝分裂的阻滞。我们发现，无法满足 SAC 的构巢曲霉细胞在经历了一段特定的有丝分裂阻滞后会使检查点失活。这种 SAC 的失活允许正常的核重组和有丝分裂退出，而不会发生 DNA 分离。我们证明，控制这种 SAC 失活的机制需要蛋白质合成，并且可以独立于主要有丝分裂调节剂 Cdk1/Cyclin B 的失活或有丝分裂退出而发生。此外，在纺锤体功能持续缺失的情况下，细胞会经历多个细胞周期，在每个有丝分裂前，SAC 都会被重新激活，然后再次失活。SAC 的这种周期性激活和失活表明，它受到独立于双极纺锤体功能的细胞周期调控。
