The fission yeast S-phase cyclin Cig2 can drive mitosis.
The fission yeast S-phase cyclin Cig2 can drive mitosis.
复制标题
裂殖酵母 S 期细胞周期蛋白 Cig2 可以驱动有丝分裂。
DOI：
10.1093/genetics/iyaa002
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发表时间：
2021
期刊：
影响因子：
3.3
通讯作者：
Rhind,Nicholas
中科院分区：
文献类型：
--
作者：
Pickering,Mary;Magner,Mira;Keifenheim,Dan;Rhind,Nicholas
细胞周期蛋白依赖性激酶（CDK）活性调节有丝分裂。在分裂酵母分裂糖酵母中，主要的b型细胞周期蛋白Cdc13是驱动有丝分裂进入的必要和充分的。此外，Cdc13也足以驱动S期，这表明单个周期蛋白可以调节交替的复制和有丝分裂，为CDK功能的定量模型提供了基础。Cig2是一种仅在S期表达且在野生型细胞中不能驱动有丝分裂的b型细胞周期蛋白，一直被认为是专门用于S期调控的。在这里，我们证明Cig2能够驱动有丝分裂。Cig2/CDK活性驱动有丝分裂突变-在不可避免的小细胞中-在酪氨酸磷酸化缺乏CDK抑制的细胞中-致命的有丝分裂。此外，在缺乏Cdc13/CDK活性的情况下，Cig2/CDK可以驱动有丝分裂，并且Cig2的组成表达可以挽救Cdc13活性的丧失。这些结果表明，在裂变酵母中，不仅假定的M期周期蛋白可以驱动S期，假定的S期周期蛋白也可以驱动M期，进一步支持CDK功能的定量模型。此外，这些结果为表达单链Cdc13-Cdc2 - CDK的细胞不需要Y15磷酸化来维持生存这一令人惊讶的观察结果提供了先前基于计算分析提出的解释。它们的生存能力是由于在这些缺乏Cig2/CDK复合物的细胞中，Cdc13/CDK活性无法驱动有丝分裂灾难。
Commitment to mitosis is regulated by cyclin-dependent kinase (CDK) activity. In the fission yeastSchizosaccharomyces pombe, the major B-type cyclin, Cdc13, is necessary and sufficient to drive mitotic entry. Furthermore, Cdc13 is also sufficient to drive S phase, demonstrating that a single cyclin can regulate alternating rounds of replication and mitosis, and providing the foundation of the quantitative model of CDK function. It has been assumed that Cig2, a B-type cyclin expressed only during S phase and incapable of driving mitosis in wild-type cells, was specialized for S-phase regulation. Here, we show that Cig2 is capable of driving mitosis. Cig2/CDK activity drives mitotic catastrophe—lethal mitosis in inviably small cells—in cells that lack CDK inhibition by tyrosine-phosphorylation. Moreover, Cig2/CDK can drive mitosis in the absence of Cdc13/CDK activity and constitutive expression of Cig2 can rescue loss of Cdc13 activity. These results demonstrate that in fission yeast, not only can the presumptive M-phase cyclin drive S phase, but the presumptive S-phase cyclin can drive M phase, further supporting the quantitative model of CDK function. Furthermore, these results provide an explanation, previously proposed on the basis of computational analyses, for the surprising observation that cells expressing a single-chain Cdc13-Cdc2 CDK do not require Y15 phosphorylation for viability. Their viability is due to the fact that in such cells, which lack Cig2/CDK complexes, Cdc13/CDK activity is unable to drive mitotic catastrophe.