MECHANISMS OF DNA REPLICATION AND RECOMBINATION IN HSV-1

描述(申请人提供)：我们正在研究单纯疱疹病毒1型(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，像真核染色体一样，HSV-1基因组包含多个复制来源。HSV-1基因组的复制是由几种病毒编码的蛋白质协同作用介导的，这些蛋白质被认为组装成一个多蛋白复合体。一些宿主编码的因子也与病毒DNA复制有关。此外，HSV-1基因组的复制与同源重组密切相关，同源重组可能在基因组末端的复制、DNA复制的启动和维持基因组的稳定性方面发挥作用。HSV-1也是典型的疱疹病毒，因此可以作为一个模型来理解这类病毒的复制机制。在这方面，HSV-1是已知的八种人类疱疹病毒之一，可导致从唇疱疹和水痘到单核细胞增多症甚至癌症等各种疾病。疱疹病毒在人类人群中的高发病率以及免疫受损个体对这些病毒的易感性增加，使其成为一个非常重要的公共卫生问题。特别是HSV-1是口腔唇部损伤的原因，以及更严重的脑炎和角膜！失明。在这一资助期间，我们建议研究病毒重组的各个方面及其在病毒复制周期中的作用，病毒复制是如何在起点启动的，以及领先和滞后的链合成是如何在病毒复制分叉上协调的。总的来说，拟议的研究将为这种具有重要医学意义和生物学吸引力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基本机制的全面了解。

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.