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

细胞周期依赖的转录波动已被观察到的所有三类核RNA聚合酶。与细胞周期相关的许多生物学事件使其成为研究基因活性与细胞周期控制之间的调节机制的有吸引力的模型。核糖体RNA基因（rDNA）代表了一个有吸引力的模型来研究这些基本过程，因为它们的活性在细胞周期中振荡。rDNA转录在S期和G2期最高，在有丝分裂期关闭，在G1期缓慢恢复。转录失活伴随着两个基础Pol I转录因子（例如SL 1和UBF）的可逆磷酸化。本研究项目的目标是详细分析抑制基础因子SL 1和UBF的分子机制，鉴定细胞蛋白磷酸酶，对抗转录因子的有丝分裂失活，绘制磷酸化氨基酸图谱，并分析相应靶位点特异性突变的功能后果。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rDNA启动子处转录复合物组装所涉及的蛋白质-蛋白质相互作用的影响。此外，我们将研究pRb和p130介导的抑制Pol I转录的生理意义。

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.