FUNCTIONS OF EBNA-1 IN THE STABLE REPLICATION OF EBV

EBNA-1在EBV稳定复制中的作用

• 批准号: 2881549
• 负责人: Ashok A Aiyar
• 金额: $ 0.35万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 1999-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2881549
• 关键词: Burkitt's lymphoma; DNA replication origin; Epstein Barr virus; Saccharomyces cerevisiae; human tissue; neoplasm /cancer genetics; plasmids; tissue /cell culture; virus antigen; virus genetics; virus protein; virus replication

I will continue ongoing studies designed to characterize the mechanism by which the Epstein-Barr nuclear antigen 1 (EBNA-1) protein of Epstein-Barr virus (EBV) facilitates the stable replication of plasmids that bear oriP, EBV's plasmid origin of replication. Together my post-doctoral mentor, Dr. Bill Sugden, and I have demonstrated that oriP-plasmids are synthesized directly by the cell, and that EBNA-1 functions post- synthetically to stabilize oriP-plasmids. Our work also demonstrates that human cells can actively eliminate extra- chromosomal DNAs. This application experimentally addresses the process by which human cells eliminate plasmids, by defining when it occurs in the cell-cycle, and understanding the mechanism by which those viruses that maintain their genomes as plasmids in human cells overcome it. It also experimentally addresses the mechanism by which oriP-plasmids are stabilized so that they can be partitioned faithfully to daughter cells, and the contributions of EBNA-1 to these processes.

我将继续正在进行的研究，旨在表征EB病毒（EBV）的EB核抗原1（EBNA-1）蛋白促进携带oriP（EBV的质粒复制起点）的质粒稳定复制的机制。 我和我的博士后导师Bill Sugden博士一起证明了oriP质粒直接由细胞合成，EBNA-1在合成后起稳定oriP质粒的作用。 我们的工作也证明了人类细胞可以主动清除染色体外的DNA. 本申请通过定义质粒在细胞周期中何时发生，并理解在人细胞中保持其基因组为质粒的那些病毒克服质粒的机制，实验性地解决了人细胞消除质粒的过程。本申请还实验性地解决了oriP-质粒稳定化的机制，从而使它们可以忠实地分配给子细胞，以及EBNA-1对这些过程的贡献。