MECHANISMS OF VIRAL CARCINOGENESIS

病毒致癌机制

• 批准号: 6101791
• 负责人: THOMAS J. KELLY
• 金额: $ 32.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-04-01 至 2000-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6101791
• 关键词: DNA binding protein; DNA directed DNA polymerase; DNA footprinting; DNA replication; DNA replication origin; DNA topoisomerases; Schizosaccharomyces pombe; biological models; cell cycle; cell free system; cell growth regulation; fungal genetics; oncogenic virus; phosphorylation; plasmids; protein kinase; simian virus 40; southern blotting; tissue /cell culture; viral carcinogenesis; virus DNA; virus genetics; virus protein; virus replication

The long-term goal of the proposed research is to contribute to an understanding of the molecular mechanisms involved in the replication of chromosomes in eukaryotic cells, particularly the mechanisms responsible for regulating DNA replication during the cell cycle. This goal is a fundamental aspect of the more general objective of the Program to understand the basic mechanisms that control cellular growth and how these mechanisms are perturbed neoplastic and virus-transformed cells. Our approach to this problem involves biochemical and genetic analysis of two experimental systems. First, we will continue our studies of the replication of the simple chromosome of the DNA tumor virus, SV4O. We plan to focus our efforts on the initiation of SV4O DNA replication in a mammalian cell-free system with particular emphasis on the role of phosphorylation of viral and cellular proteins in controlling the initiation process. Second, we will employ the fission yeast, Schizosaccharomyces pombe as a model system to explore the mechanisms involved in initiating DNA replication at cellular origins. We plan to define the essential genetic elements required for origin function and to identify and characterize the cellular initiator proteins that interact with such elements.

拟议研究的长期目标是为 了解复制的分子机制 真核细胞中的染色体，特别是负责的机制 用于调节细胞周期中的DNA复制。这个目标是 该计划更一般目标的基本方面 了解控制细胞生长的基本机制以及如何 机理是扰动的肿瘤和病毒转化的细胞。我们的 解决此问题的方法涉及两个的生化和遗传分析 实验系统。首先，我们将继续研究 DNA肿瘤病毒的简单染色体SV4O的复制。我们计划 将我们的精力集中在启动SV4O DNA复制上 哺乳动物无细胞系统，特别强调 病毒和细胞蛋白的磷酸化控制 启动过程。其次，我们将采用裂变酵母， 精神分裂症pombe作为探索机制的模型系统 涉及在细胞起源处启动DNA复制。我们计划 定义原始功能所需的必需遗传元素和 识别和表征相互作用的细胞引发剂蛋白 有这样的元素。