MECHANISMS OF DNA REPLICATION AND RECOMBINATION IN HSV-1

描述（由申请人提供）：我们正在研究1型单纯疱疹病毒（HSV-1）复制和重组的分子机制。HSV-1是研究DNA交易的一个很好的系统。因此，与真核染色体一样，HSV-1基因组含有多个复制起点。HSV-1基因组的复制是由几种病毒编码蛋白的协同作用介导的，这些蛋白被认为组装成多蛋白复合物。一些宿主编码的因子也与病毒DNA复制有关。此外，已知HSV-1基因组的复制与同源重组密切相关，所述同源重组可在基因组末端的复制、DNA复制的起始和维持基因组稳定性中起作用。HSV-1也是疱疹病毒的原型，因此可以作为了解这类病毒复制机制的模型。在这方面，HSV-1是已知引起从唇疱疹和水痘到单核细胞增多症甚至癌症的多种疾病的八种人类疱疹病毒之一。疱疹病毒在人群中的高发病率和免疫受损个体对这些病毒的易感性增加使其成为非常重要的公共卫生问题。特别是HSV-1是口唇病变以及更严重的脑炎和角膜的原因！失明在此期间，我们建议研究病毒重组及其在病毒复制周期中的作用，病毒复制如何在起点启动，以及前导链和滞后链的合成如何在病毒复制叉处协调。总的来说，拟议的研究将为这种医学上重要的和生物学上迷人的病毒的复制提供新的见解。它们还将增加我们对复制和重组的基本机制的整体知识。

DESCRIPTION (provided by applicant): We are studying molecular mechanisms of replication and recombination in herpes simplex virus type-1 (HSV-1). HSV-1 serves as an excellent system in which to study DNA transactions. Hence, like eukaryotic chromosomes, the HSV-1 genome contains multiple origins of replication. Replication of the HSV-1 genome is mediated by the concerted action of several virus-encoded proteins that are thought to assemble into a multiprotein complex. Several host-encoded factors have also been implicated in viral DNA replication. Furthermore, replication of the HSV-1 genome is known to be closely associated with homologous recombination which may function in replication of genomic termini, in initiation of DNA replication and in maintaining genome stability. HSV-1 is also the prototypic herpesvirus and therefore serves as a model to understand the mechanism of replication of this class of virus. In this regard, HSV-1 is one of eight human herpesviruses that are know to cause diverse diseases ranging from cold sores and chicken pox to mononucleosis and even cancer. The high incidence of herpesviruses in the human population and the increased susceptibility of immuno-compromised individuals to these viruses make them a very important public health problem. HSV-1 in particular is the cause of oro-labial lesions as well as more serious encephalitis and cornea! blindness. In this grant period, we propose to examine aspects of viral recombination and its role in the viral replicative cycle, how viral replication initiates at an origin, and how leading and lagging strand synthesis are coordinated at the viral replication fork. Collectively, the proposed studies will provide novel insight into the replication of this medically important and biologically fascinating virus. They will also increase our overall knowledge of fundamental mechanisms in replication and recombination.