MECHANISMS OF VIRAL CARCINOGENESIS

拟议研究的长期目标是为 了解复制过程中涉及的分子机制 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。这个目标是一个 该计划更一般目标的基本方面是 了解控制细胞生长的基本机制以及这些机制是如何 机制是受干扰的肿瘤细胞和病毒转化的细胞。我们的 解决这个问题的方法包括对两种生物化学和基因分析 实验系统。首先，我们将继续研究 复制DNA肿瘤病毒SV4O的简单染色体。我们计划 将我们的努力集中在启动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在控制病毒中的作用 启动过程。第二，我们将使用分裂酵母， 以裂殖酵母为模型系统探讨其作用机制 参与在细胞起始处启动DNA复制。我们计划 定义起源功能所需的基本遗传要素 鉴定和鉴定相互作用的细胞启动蛋白 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.