Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, CH-1015 Lausanne, Switzerland.
Genetics. 2010 Dec;186(4):1271-83. doi: 10.1534/genetics.110.123133. Epub 2010 Oct 13.
The anaphase promoting complex/cyclosome (APC/C) triggers the separation of sister chromatids and exit from mitosis across eukaryotic evolution. The APC/C is inhibited by the spindle assembly checkpoint (SAC) until all chromosomes have achieved bipolar attachment, but whether the APC/C reciprocally regulates the SAC is less understood. Here, we report the characterization of a novel allele of the APC5 component SUCH-1 in Caenorhabditis elegans. We find that some such-1(t1668) embryos lack paternally contributed DNA and centrioles and assemble a monopolar spindle in the one-cell stage. Importantly, we show that mitosis is drastically prolonged in these embryos, as well as in embryos that are otherwise compromised for APC/C function and assemble a monopolar spindle. This increased duration of mitosis is dependent on the SAC, since inactivation of the SAC components MDF-1/MAD1 or MDF-2/MAD2 rescues proper timing in these embryos. Moreover, partial depletion of the E1 enzyme uba-1 significantly increases mitosis duration upon monopolar spindle assembly. Taken together, our findings raise the possibility that the APC/C negatively regulates the SAC and, therefore, that the SAC and the APC/C have a mutual antagonistic relationship in C. elegans embryos.
后期促进复合物/细胞周期蛋白体(APC/C)在真核生物进化过程中触发姐妹染色单体的分离和有丝分裂的退出。APC/C 被纺锤体组装检查点(SAC)抑制,直到所有染色体都实现双极连接,但 APC/C 是否反过来调节 SAC 知之甚少。在这里,我们报告了秀丽隐杆线虫 APC5 成分 SUCH-1 的一种新型等位基因的特征。我们发现,一些 such-1(t1668)胚胎缺乏父本贡献的 DNA 和中心粒,并在单细胞阶段组装出一个单极纺锤体。重要的是,我们表明,这些胚胎中的有丝分裂时间明显延长,而在 APC/C 功能受到其他影响并组装出单极纺锤体的胚胎中也是如此。这种有丝分裂持续时间的延长依赖于 SAC,因为 SAC 成分 MDF-1/MAD1 或 MDF-2/MAD2 的失活可以挽救这些胚胎中的适当时间。此外,uba-1 的 E1 酶部分耗尽在单极纺锤体组装时显著增加有丝分裂时间。总之,我们的发现提出了 APC/C 负调节 SAC 的可能性,因此 SAC 和 APC/C 在秀丽隐杆线虫胚胎中具有相互拮抗的关系。