REGULATION OF DNA REPLICATION AND CELL GROWTH

因为真核细胞生长控制的调控密切相关 与DNA复制的调控有关，完全理解 没有理解，就不能实现增长控制调控 DNA复制的调控。相反，理解规则的规则 复制将有助于定义由蛋白质编码的信号通路 “核致癌基因”。我们计划的总体目标是定义 调控DNA复制启动所需的要素，来自 核癌基因产物通过DNA序列和 复制起点的结构。 该计划由4个项目组成，每个项目由一名调查员领导， 不同但互补的专业知识，每个专业知识都专注于不同的、 但与复制控制相关的方面。其中两个项目涉及 核癌基因的研究。在其中一个项目中，核能 在不同阶段调节细胞生长的癌基因 胚胎发育将被确定，突变或 这些基因在DNA复制模式和细胞上的过度表达 用于复制一个特定的核癌基因c-myc的增殖 基因，将被定位，在这个起源地的重要DNA序列将是 鉴定，与这些重要序列结合的蛋白质将被 分离并检测其生物活性。 另外两个项目将提供有关以下方面的详细信息 复制起点的结构和功能。在其中一个项目中， 人类DNA序列中的基本序列元素，可以取代 Epstein-Barr病毒(EBV)序列以产生功能性EBV复制 将绘制起源图，即与这些基本序列结合的蛋白质 将被分离出来，人类对EBV功能至关重要的基因- 将定义起源互补的人类序列。在另一方 项目，假设一段容易解开的DNA(DNA 展开元素；到期)是将由测试的基本原始组件 酵母复制起始点的详细序列和结构分析 上面讨论的c-myc和EBV复制起源。

Because regulation of growth control in eukaryotic cells is intimately connected with regulation of DNA replication, complete understanding of growth control regulation cannot be achieved without understanding regulation of DNA replication. Conversely, understanding the regulation of replication will help define the signaling pathways is proteins encoded by "nuclear oncogenes". The overall objective of our program is to define the elements required for regulating the initiation of DNA replication, from the actions of nuclear oncogene products through the DNA sequence and structures of replication origins. This program consists of 4 projects, each headed by an investigator with different, but complementary, expertise and each focussed on a different, but related, aspect of replication control. Two of the projects involve study of nuclear oncogenes. In one of these projects, the nuclear oncogenes which function to regulate cell growth during different stages of embryonic development will be identified, and the effects of mutation or overexpression of these genes on DNA replication patterns and cell proliferation for replicating one particular nuclear oncogene, the c-myc gene, will be located, the important DNA sequences at this origin will be identified, and proteins which bind to these important sequences will be isolated and tested for biological activity. The other two projects will provide detailed information about aspects of replication origin structure and function. In one of these projects, the essential sequence elements within human DNA sequences which can replace an Epstein-Barr virus (EBV) sequence to generate a functional EBV replication origin will be mapped, proteins which bind to these essential sequences will be isolated, and human genes essential for the function of the EBV- origin-complementing human sequences will be defined. In the other project, the hypothesis that an easily unwound stretch of DNA (DNA Unwinding Element; DUE) is an essential origin component will be tested by detailed sequence and structural analysis of yeast replication origins and the c-myc and EBV replication origins discussed above.