INTERACTIONS OF THE MCM PROTEINS AT REPLICATION ORIGINS

DNA合成的启动是一个复杂的多步骤过程， 需要多个复制启动的协调操作 各种因素。这一过程始于有序地组装一个预置 G1期复制起始处的复制复合体(Pre-RC)。 对酿酒酵母的研究表明，前RC包括 进化上保守的复制启动因子，包括 起源识别复合体，ORC，一种同胞亚基的复合体，以及 MCM2-7蛋白是一个由六个同源蛋白组成的家族。DNA的启动 合成是由成分的连续磷酸化激活的。 至少两个CDK(细胞周期蛋白依赖性蛋白激酶)或CDK- 和激酶一样，CDC28-Clb和CDC-7-Dbf4。DNA合成的起始位置 复制起点伴随着从前RC到 伸长复合体。随着伸长复合体从 复制源，复制前的RC被复制后的RC替换 复杂(后RC)，似乎包括ORC，但不包括另一个 Pre-RC的已知组件。先前的研究表明，Mcm10 在物理上与McM2-7蛋白的成员相互作用。我们会 研究Mcm10在装配和拆卸中的多重作用 Pre-Rc及其在延伸型式迁移中的作用 与McM2-7蛋白结合。还将做出重大努力 致力于分析Mcm10和McM10之间的功能关系 Pre-RC的其他组件。这些研究应该提供信息 关于将DNA合成限制在一个细胞周期一次的机制 在真核生物中。癌细胞的特点是它们的细胞不受调控 组织。这项研究解决了控制空气污染的一个基本问题。 酿酒酵母的DNA复制和细胞分裂 模特。通过了解正常的细胞过程来调节 DNA复制，就有可能阐明 导致癌细胞处于疾病状态的异常或缺陷。

The initiation of DNA synthesis is a complex multi-step process that requires the coordinated actions of a number of replication initiation factors. This process begins with the ordered assembly of a pre- replication complex (pre-RC) at replication origins during the G1 phase. Studies in Saccharomyces cerevisiae indicate that the pre-RC consists of evolutionarily conserved replication initiation factors that include the origin recognition complex, ORC, a complex of sib subunits, and the Mcm2-7 proteins, a family of six homologous proteins. Initiation of DNA synthesis is activated by the successive phosphorylations of components of the pre-RC by at least two Cdks (cyclin dependent kinases) or Cdk- like kinases, Cdc28-Clb and Cdc-7-Dbf4. Initiation of DNA synthesis at replication origins is accompanied by a transition of the pre-RC to the elongation complex. As the elongation complex migrates away from the replication origin, the pre-RC is replaced by the post-replication complex (post-RC), which appears to include the ORC but not the other known components of the pre-RC. Previous studies showed that Mcm10 physically interacts with members of the Mcm2-7 proteins. We will investigate the multiple roles of Mcm10 in the assembly and disassembly of the pre-RC and its role in the migration of elongation forms in conjunction with the Mcm2-7 proteins. Significant efforts will also be devoted to the analysis of the functional relationship between Mcm10 and other components of the pre-RC. These studies should provide information about the mechanism that restricts DNA synthesis to once per cell cycle in eukaryotes. Cancer cells are characterized by their unregulated cell divisions. This study addresses a fundamental problem in the control of DNA replication and cell division using Saccharomyces cerevisiae as the model. Through understanding of normal cellular processes that regulate DNA replication, it may be possible to elucidate the molecular basis for abnormalities or defects that lead to the disease state in cancer cells.