The control of the initiation step of DNA replication by proteinkinase Dbf4/Cdc7 Regulation des murinen "origin recognition complex (ORC)" durch Cyclin-Cdk-Komplexe

蛋白激酶 Dbf4/Cdc7 对 DNA 复制起始步骤的控制 细胞周期蛋白-Cdk 复合物对小鼠“起源识别复合物 (ORC)”的调节

• 批准号: 5225882
• 负责人: Professor Dr. Friedrich Grummt (†)
• 金额: --
• 依托单位: Lehrstuhl für Biochemie I
• 依托单位国家: 德国
• 项目类别: Priority Programmes
• 财政年份: 1995
• 资助国家: 德国
• 起止时间: 1994-12-31 至 2001-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/5225882?language=en
• 关键词: control; initiation; step; DNA; replication

Our particular long-term aim is the elucidation of the molecular mechanisms governing the onset of DNA replication at the G1/S phase transition. The project we are seeking support for will be focussed on the particular role played by the protein kinase complex Dbf4/Cdc7 during the transition from the G1 to the S phase of the cell cycle and its dependence on the mitogenic signal transduction cascade. Specifically, we will investigate the following aspects: (i) effects of interactions between Dbf4p and Cdc7p on kinase activity and structural analysis of interacting domains, (ii) analysis of phosphorylation sites in Dbf4/Cdc7p and their point mutation (iii) functional effects of phosphorylation of Dbf4/cdc7p by cyclin/Cdks and by autophosphorylation, (iv) characterization of targets of Dbf4/Cdc7p kinase activity, (v) generation of conditional knock-out mice for the analysis of functions of Dbf4/Cdc7 in cell proliferation and differentiation. We expect that these studies will lead to a general understanding of the mechanism by which Dbf4/Cdc7 contributes to initiation of DNA replication and cell cycle control.

我们的长期目标是阐明在G1/S相变时DNA复制开始的分子机制。我们正在寻求支持的项目将集中在蛋白激酶复合物Dbf 4/Cdc 7在细胞周期从G1期过渡到S期期间所发挥的特殊作用及其对促有丝分裂信号转导级联的依赖性。具体而言，我们将调查以下几个方面：（i）Dbf 4 p和Cdc 7 p之间的相互作用对激酶活性的影响和相互作用结构域的结构分析，（ii）Dbf 4/Cdc 7 p中的磷酸化位点及其点突变的分析，（iii）通过细胞周期蛋白/Cdks和通过自磷酸化对Dbf 4/Cdc 7 p的磷酸化的功能影响，（iv）Dbf 4/Cdc 7 p激酶活性的靶标的表征，（v）产生条件性敲除小鼠，用于分析Dbf 4/Cdc 7在细胞增殖和分化中的功能。我们期望这些研究将导致对Dbf 4/Cdc 7有助于启动DNA复制和细胞周期控制的机制的普遍理解。