MECHANISMS OF VIRAL CARCINOGENESIS

拟议研究的长期目标是促进 了解参与复制的分子机制， 真核细胞中的染色体，特别是负责 在细胞周期中调节DNA复制。这个目标是一个 该方案更一般目标的基本方面， 了解控制细胞生长的基本机制，以及这些机制如何 机制是扰动的肿瘤细胞和病毒转化细胞。我们 解决这个问题的方法涉及两种生物化学和遗传分析， 实验系统首先，我们将继续研究 DNA肿瘤病毒SV4O的简单染色体的复制。我们计划 我们的工作重点是启动SV4O DNA复制， 哺乳动物无细胞系统，特别强调 病毒和细胞蛋白的磷酸化， 启动过程。其次，我们将使用裂变酵母， 以粟酒裂殖酵母为模式系统探讨其作用机制 参与启动细胞起源处的DNA复制。我们计划 确定起源功能所需的基本遗传元件， 鉴定和表征相互作用的细胞起始蛋白 有这样的元素。

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.