HUMAN GENOME REPLICATION

人类基因组复制

• 批准号: 6299965
• 负责人: BRUCE S STILLMAN
• 金额: $ 37.41万
• 依托单位: COLD SPRING HARBOR LABORATORY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-01-01 至 2000-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6299965
• 关键词: DNA binding protein; DNA replication; DNA replication origin; Drosophilidae; biochemical evolution; cell cycle proteins; cell growth regulation; cell transformation; chromatography; fluorescent in situ hybridization; genetic mapping; genetic regulatory element; human genetic material tag; laboratory mouse; laboratory rabbit; molecular oncology; nucleic acid sequence; protein purification; protein sequence; protein structure function; tissue /cell culture; yeast two hybrid system

One of the key events in the cell division cycle is the initiation of chromosomal DNA replication and it is likely that the control of this process in human tumor cells are abnormal. Unfortunately, little is known about the mechanism of initiation of DNA replication in any metazoan species. This project will expand upon an important discovery of a candidate DNA initiator protein that may play a key role in the initiation of chromosomal DNA replication in human cells. The specific goals of the project will be to identify all of the subunits of the human Origin Recognition Complex (hORC) and to study their functions in vitro and in vivo. The sites in the human genome to which hORC binds will be characterized and mapped to regions known to contain origins of DNA replication. Finally proteins that interact with the hORC will be investigated and their interaction with the cell cycle regulatory machinery determined. These studies should advance our understanding of the mechanism of initiation of replication of the human genome and determine how this process is controlled during the cell division cycle. These studies are directly relevant to the overall goals of this program project.

细胞分裂周期的关键事件之一是启动 染色体 DNA 复制，并且很可能是对这种复制的控制 人类肿瘤细胞的过程是异常的。 不幸的是，很少有 已知DNA复制起始机制 后生动物种类。 该项目将扩展一个重要的 发现可能发挥关键作用的候选DNA起始蛋白 在人类染色体DNA复制起始中的作用 细胞。 该项目的具体目标是确定所有 人类起源识别复合体 (hORC) 的亚基和 研究它们的体外和体内功能。 人体中的场所 hORC 结合的基因组将被表征并映射到 已知含有 DNA 复制起点的区域。最后 将研究与 hORC 相互作用的蛋白质及其 确定与细胞周期调节机制的相互作用。 这些研究应该增进我们对该机制的理解 人类基因组复制的起始并确定如何 这个过程在细胞分裂周期中受到控制。 这些 研究与该计划的总体目标直接相关 项目。