Mechanism of cell cycle-dependent transcriptional control of RNA polymerase I Mechanismus Zellzyklus-abhängiger Transkriptionskontrolle von RNA-Polymerase I

这三类核RNA聚合酶都观察到了依赖于细胞周期的转录波动。与细胞周期相关的众多生物学事件使其成为研究基因活性与细胞周期调控调控机制的一个有吸引力的模型。核糖体RNA基因(RDNA)是研究这类基本过程的一个有吸引力的模型，因为它们的活性在细胞周期中振荡。核糖核酸转录在S和G2期达到最大值，有丝分裂停止，G1期缓慢恢复。转录失活伴随着两个基本的Pol I转录因子，如SL1和UBF的可逆磷酸化。本研究的目标是详细分析基础因子SL1和UBF失活的分子机制，鉴定与转录因子有丝分裂失活有关的细胞蛋白磷酸酶(S)，定位磷酸化的氨基酸，以及分析各自靶点特定突变的功能后果。我们将研究特定的蛋白激酶和磷酸酶对RNA聚合酶I特异性转录因子活性的影响，以及它们对参与rDNA启动子转录复合体组装的蛋白质-蛋白质相互作用的影响。此外，我们还将探讨pRb和p130介导的Pol I转录抑制的生理学意义。

Cell cycle-dependent fluctuations of transcription have been observed for all three classes of nuclear RNA polymerases. The numerous biological events that are associated with the periodicity of the cell cycle make it an attractive model for the study of regulatory mechanism that link gene activity to cell cycle control. Ribosomal RNA genes (rDNA) represent an attractive model to investigate such fundamental processes, because their activity oscillates during the cell cycle. rDNA transcription is maximal in S and G2 phase, shuts down in mitosis and slowly recovers in G1. Transcriptional inactivation is accompanied by reversible phosphorylation of two basal Pol I transcription factors, e.g. SL1 and UBF. The goal of this research project is a detailed analysis of the molecular mechanisms that inactivate the basal factors SL1 and UBF, the identification of the cellular protein phosphatase(s) that counteract mitotic inactivation of transcription factors, mapping of phosphorylated amino acids, and the analysis of functional consequences of specific mutation of the respective target sites. We will study the influence of specific protein kinases and phosphatases on the activity of RNA polymerase I-specific transcription factors as well as their effects on protein-protein interactions that are involved in transcription complex assembly at the rDNA promoter. Moreover, we are going to investigate the physiological significance of pRb- and p130-mediated repression of Pol I transcription.