Mutual Antagonism Between the Anaphase Promoting Complex and the Spindle Assembly Checkpoint Contributes to Mitotic Timing in Caenorhabditis elegans
Mutual Antagonism Between the Anaphase Promoting Complex and the Spindle Assembly Checkpoint Contributes to Mitotic Timing in Caenorhabditis elegans
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DOI：
10.1534/genetics.110.123133
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发表时间：
2010-12-01
期刊：
影响因子：
3.3
通讯作者：
Goenczy, Pierre
中科院分区：
文献类型：
--
作者：
Bezler, Alexandra;Goenczy, Pierre
在真核生物进化过程中，后期促进复合体/细胞周期体（APC/C）触发姐妹染色单体的分离并退出有丝分裂。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附着，但APC/C是否调节SAC还不太清楚。在这里，我们报告的APC 5组件SUCH-1在秀丽隐杆线虫的一个新的等位基因的特性。我们发现，一些这样的-1（t1668）胚胎缺乏父系贡献的DNA和中心粒和组装单极纺锤体在单细胞阶段。重要的是，我们表明，有丝分裂在这些胚胎中大大延长，以及在胚胎中，否则APC/C功能受损，并组装单极纺锤体。这种增加的有丝分裂持续时间依赖于SAC，因为SAC组分MAD 1/MAD 1或MAD 2/MAD 2的失活挽救了这些胚胎中的适当时机。此外，E1酶乌巴-1的部分消耗显着增加有丝分裂持续时间后单极纺锤体组装。综上所述，我们的研究结果提出了APC/C负调控SAC的可能性，因此，SAC和APC/C在C中具有相互拮抗的关系。线虫胚胎
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.