MECHANISMS OF DNA REPLICATION AND RECOMBINATION IN HSV-1

HSV-1 中 DNA 复制和重组的机制

• 批准号: 7326613
• 负责人: Paul E Boehmer
• 金额: $ 25.2万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 1996
• 资助国家: 美国
• 起止时间: 1996-06-01 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7326613
• 关键词: DNA binding protein; DNA replication; DNA replication origin; DNA topoisomerases; gel electrophoresis; genetic recombination; helicase; herpes simplex virus 1; host organism interaction; intermolecular interaction; nucleic acid hybridization; oligonucleotides; radiotracer; virus DNA; virus genetics; virus protein

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.

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 交易的优秀系统。因此，与真核染色体一样，HSV-1 基因组包含多个复制起点。 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，同源重组可能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发挥作用。 HSV-1 也是典型的疱疹病毒，因此可作为了解此类病毒复制机制的模型。在这方面，HSV-1 是已知可引起唇疱疹、水痘、单核细胞增多症甚至癌症等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以及免疫功能低下的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。 HSV-1 尤其是导致口腔唇部病变以及更严重的脑炎和角膜炎的原因！失明。在此资助期内，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，病毒复制如何从起点开始，以及前导链和滞后链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具有医学重要性和生物学意义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整体了解。