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后期促进复合物与纺锤体组装检查点之间的相互拮抗作用有助于秀丽隐杆线虫有丝分裂时间的调控。

Mutual antagonism between the anaphase promoting complex and the spindle assembly checkpoint contributes to mitotic timing in Caenorhabditis elegans.

机构信息

Swiss Institute for Experimental Cancer Research, School of Life Sciences, Swiss Federal Institute of Technology, CH-1015 Lausanne, Switzerland.

出版信息

Genetics. 2010 Dec;186(4):1271-83. doi: 10.1534/genetics.110.123133. Epub 2010 Oct 13.

Abstract

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.

摘要

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。

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