Chromosome segregation and cyclin degradation in the cell cycle of eukaryotic microorganisms Chromosomen-Segregation und Cyclin-Degradation im Zellzyklus eukaryontischer Mikroorganismen

在真核生物有丝分裂过程中，由泛素连接酶--后期促进复合体(APC)启动的蛋白质降解是一种重要且高度保守的机制。APC的活性需要在细胞周期中受到精确的调控。它在中期的激活触发姐妹染色单体的分离，随后在有丝分裂周期蛋白的有丝分裂蛋白分解中，导致细胞周期蛋白依赖的激酶失活和有丝分裂退出。在这个项目中，我们将分析APC功能在酵母细胞分裂中的调节因素和机制。我们主要集中在进一步研究RAS/cAMP/PKA通路如何介导APC活性的抑制，核转运对APC功能的作用，以及晚期有丝分裂基因如何在末期被激活，从而诱导APC触发周期蛋白分解。我们还将研究APC在不同的细胞分化过程中的作用及其调控，特别是在酵母的孢子形成和假菌丝形成过程中。此外，我们将我们的实验扩展到丝状真菌nidulans，以分析APC的功能及其在更复杂的细胞分化过程中的调节，如子实体形成。

Proteolytic degradation initiated by the anaphase- promoting complex (APC), a ubiquitin-ligase, is a crucial and highly conserved mechanism during mitosis in eukaryotes. The activity of the APC needs to be precisely regulated during the cell cycle. Its activation at metaphase triggers sister chromatid separation and later in mitosis proteolysis of mitotic cyclins, resulting in cyclin-dependent kinase inactivation and mitotic exit. In this project we will analyse factors and mechanisms involved in the regulation of APC function in dividing yeast cells. We are mainly focused on a further characterisation of how the Ras/cAMP/PKA pathway mediates inhibition of APC activity, the role of nuclear transport for APC function and how late mitotic genes are activated at telophase, thereby inducing the APC to trigger cyclin proteolysis. We will also study the role of the APC and its regulation in different cellular differentiation processes, particularily during sporulation and pseudohyphae formation in yeast. In addition, we extend our experiments to the filamentous fungus Aspergillus nidulans to analyse the function of the APC and its regulation in more complex cellular differentiation processes like fruitbody formation.