STRUCTURE & FUNCTION OF A CMV ORIGIN OF DNA REPLICATION

描述：人巨细胞病毒（HCMV）是一种常见的机会致病菌， 广泛的发病率和死亡率。 这是艾滋病的一个特殊问题 患者，并可能是艾滋病毒发病机制的辅助因子。 更好的 了解HCMV DNA复制的分子机制， 需要进行监管，以帮助制定抗病毒战略。 裂解相 DNA复制需要一个基因定义的顺式作用复制因子， oriLyt和反式作用因子如病毒特异性DNA聚合酶。 先前的研究导致了HCMV机制模型的发展 oriLyt起始;在该模型中，转录本促进了 通过促进oriLyt内的链分离来预起始复合物。 这项建议的具体目标是：1）更好地建立 使用标准的oriLyt序列内的必需元件的结构 分子遗传学方法; 2）确定顺式作用元件 参与调节oriLyt转录本表达，并鉴定其 同源激活物; 3）测试申请人的起始转录物模型， IE 2/oriLyt的启动机制; 4）测试IE 2/oriLyt的作用 复制因子功能中的相互作用。

DESCRIPTION: Human CMV (HCMV) is a frequent opportunistic pathogen, causing extensive morbidity and mortality. It is a particular problem in AIDS patients, and may be a cofactor for HIV pathogenesis. A better understanding of the molecular mechanisms of HCMV DNA replication and their regulation is needed to aid in developing antiviral strategies. Lytic-phase DNA replication requires both a genetically defined cis-acting replicator, oriLyt, and trans-acting factors such as the virus-specified DNA polymerase. Previous studies led to the development of a model for the mechanism of HCMV oriLyt initiation; in this model a transcript facilitates the assembly of the pre-initiation complex by promoting strand-separation within oriLyt. The specific aims of this proposal are: 1) to better establish the structures of essential elements within the oriLyt sequence using standard molecular genetic approaches; 2) to determine the cis-acting elements involved in regulating oriLyt transcript expression, and identify their cognate activators; 3) to test the applicant s initiator transcript model of the mechanism of initiation; and 4) to test the role of IE2/oriLyt interactions in replicator function.