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Dma1 介导的检查点的缓解需要 Dma1 自身泛素化和动态定位。

Relief of the Dma1-mediated checkpoint requires Dma1 autoubiquitination and dynamic localization.

机构信息

Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, TN 37240.

出版信息

Mol Biol Cell. 2018 Sep 1;29(18):2176-2189. doi: 10.1091/mbc.E18-04-0261. Epub 2018 Jul 5.

Abstract

Chromosome segregation and cell division are coupled to prevent aneuploidy and cell death. In the fission yeast Schizosaccharomyces pombe, the septation initiation network (SIN) promotes cytokinesis, but upon mitotic checkpoint activation, the SIN is actively inhibited to prevent cytokinesis from occurring before chromosomes have safely segregated. SIN inhibition during the mitotic checkpoint is mediated by the E3 ubiquitin ligase Dma1. Dma1 binds to the CK1-phosphorylated SIN scaffold protein Sid4 at the spindle pole body (SPB), and ubiquitinates it. Sid4 ubiquitination antagonizes the SPB localization of the Pololike kinase Plo1, the major SIN activator, so that SIN signaling is delayed. How this checkpoint is silenced once spindle defects are resolved has not been clear. Here we establish that Dma1 transiently leaves SPBs during anaphase B due to extensive autoubiquitination. The SIN is required for Dma1 to return to SPBs later in anaphase. Blocking Dma1 removal from SPBs by permanently tethering it to Sid4 prevents SIN activation and cytokinesis. Therefore, controlling Dma1's SPB dynamics in anaphase is an essential step in S. pombe cell division and the silencing of the Dma1-dependent mitotic checkpoint.

摘要

染色体分离和细胞分裂是耦合的,以防止非整倍体和细胞死亡。在裂殖酵母 Schizosaccharomyces pombe 中,分隔起始网络(SIN)促进胞质分裂,但在有丝分裂检查点激活后,SIN 被积极抑制,以防止染色体安全分离之前发生胞质分裂。有丝分裂检查点期间的 SIN 抑制是由 E3 泛素连接酶 Dma1 介导的。Dma1 在纺锤体极体(SPB)处与 CK1 磷酸化的 SIN 支架蛋白 Sid4 结合,并泛素化它。Sid4 泛素化拮抗 Pololike 激酶 Plo1 的 SPB 定位,Plo1 是主要的 SIN 激活剂,从而延迟了 SIN 信号。一旦纺锤体缺陷得到解决,这个检查点是如何被沉默的还不清楚。在这里,我们确定 Dma1 在后期 B 期由于广泛的自泛素化而暂时离开 SPB。SIN 是 Dma1 在后期返回到 SPB 所必需的。通过将 Dma1 永久地固定在 Sid4 上阻止其从 SPB 上移除,从而阻止了 SIN 的激活和胞质分裂。因此,控制 Dma1 在后期的 SPB 动力学是 S. pombe 细胞分裂和 Dma1 依赖性有丝分裂检查点沉默的一个关键步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1ee9/6249794/23486bad760c/mbc-29-2176-g001.jpg

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