ANALYSIS OF HOMOLOGOUS RECOMBINATION IN HSV 1

这项研究计划的长期目标是界定穷人 单纯疱疹同源重组的特征性机制 1型病毒（HSV-1）。更好地了解这方面的基本 这种重要病原体的生物学特性可能有助于更有效地 治疗策略在这方面有三个具体目标 利用HSV-1 DNA复制蛋白能力的建议 介导同源重组。首先，将重组HSV-1 生成在L-S连接处缺乏α序列的细胞，并进行测试 进行基因组异构化的能力。 二、机制 同源重组诱导的双链断裂产生的 将研究EcoRI和细胞拓扑异构酶II。 最后 重组表达的HSV-1复制蛋白的能力 杆状病毒在Sf 9细胞中介导同源重组将是 检查并与HSV- 1介导的反应进行比较;该系统将 也可用于确定HSV- 1是否参与复制- 依赖性重组或重组依赖性复制。这些 结果将有助于阐明同源重组的机制 在HSV-1和nay中提供了对人类这种现象重要见解 细胞

The long-term objective of this research proposal is to define the poorly characterized mechanism of homologous recombination in Herpes Simplex Virus Type 1 (HSV-1). A better understanding of this aspect of the basic biology of this important pathogen may contribute to more effective therapeutic strategies. Three specific aims are being undertaken in this proposal that exploit the ability of the HSV-1 DNA replication proteins to mediate homologous recombination. First, a recombinant HSV-1 will be generated that lacks the alpha sequence at the L-S junction and tested for the ability to undergo genome isomerization. Second, the mechanism of homologous recombination induced by double-strand breaks generated by EcoRI and cellular topoisomerase II will be investigated. Finally, the ability of the HSV-1 replication proteins expressed by recombinant baculoviruses in Sf9 cells to mediate homologous recombination will be examined and compared with reactions mediated by HSV- 1; this system will also be used to determine if HSV- 1 participates in replication- dependent-~recombination or recombination-dependent-replication. These results will help to elucidate the mechanism of homologous recombination in HSV-1 and nay provide important insight into this phenomenon in human cells.