Genetic interactions between Cdk1-CyclinB and the separase complex in Drosophila
Genetic interactions between Cdk1-CyclinB and the separase complex in Drosophila
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DOI：
10.1242/dev.01780
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发表时间：
2005-04-01
期刊：
影响因子：
4.6
通讯作者：
Schubiger, G
中科院分区：
文献类型：
--
作者：
Ji, JY;Crest, J;Schubiger, G
Cdk 1-CycB在调节细胞周期事件的许多方面起着关键作用，例如有丝分裂期间的细胞骨架动力学和染色体行为。为了研究Cdk 1-CycB如何控制这些事件的协调，我们进行了一个剂量敏感的遗传筛选，这是基于观察，增加母体CycB（4个额外的基因拷贝）导致更高的Cdk 1-CycB活性在早期果蝇胚胎，延迟后期发作，并产生致敏的非致死性表型在胚盘阶段（定义为6个cycB表型）。在这里，我们报告说，基因三行（thr）的突变增强，而突变丘疹（pim，编码果蝇Securin）或分离酶（Sse）抑制，致敏表型。在果蝇中，已知Pim和Thr都调节Sse活性，并且激活的Sse切割一个Cohesin亚基以启动后期。与6个cycB胚胎相比，减少更多CycB胚胎中的Thr进一步延迟后期的启动，而减少Pim或Sse具有相反的效果。此外，细胞核移动速度较慢，皮质迁移在胚胎中具有较高的Cdk 1-CycB活性，而减少Pim或Sse抑制这种表型引起一种新的核迁移模式。因此，我们的遗传筛选已经确定了调节姐妹染色单体分离的复合物的所有三个组分，并且我们的观察表明Cdk 1-CycB和Pim-Thr-Sse复合物之间的相互作用是剂量敏感的。
Cdk1-CycB plays a key role in regulating many aspects of cell-cycle events, such as cytoskeletal dynamics and chromosome behavior during mitosis. To investigate how Cdk1-CycB controls the coordination of these events, we performed a dosage-sensitive genetic screen, which is based on the observations that increased maternal CycB (four extra gene copies) leads to higher Cdk1-CycB activity in early Drosophila embryos, delays anaphase onset, and generates a sensitized non-lethal phenotype at the blastoderm stage (defined as six cycB phenotype). Here, we report that mutations in the gene three rows (thr) enhance, while mutations in pimples (pim, encoding Drosophila Securin) or separase (Sse) suppress, the sensitized phenotype. In Drosophila, both Pim and Thr are known to regulate Sse activity, and activated Sse cleaves a Cohesin subunit to initiate anaphase. Compared with the six cycB embryos, reducing Thr in embryos with more CycB further delays the initiation of anaphase, whereas reducing either Pim or Sse has the opposite effect. Furthermore, nuclei move slower during cortical migration in embryos with higher Cdk1-CycB activity, whereas reducing either Pim or Sse suppresses this phenotype by causing a novel nuclear migration pattern. Therefore, our genetic screen has identified all three components of the complex that regulates sister chromatid separation, and our observations indicate that interactions between Cdk1-CycB and the Pim-Thr-Sse complex are dosage sensitive.