STRUCTURE & FUNCTION OF A CMV ORIGIN OF DNA REPLICATION

描述：人巨细胞病毒(HCMV)是一种常见的条件致病原，可引起 广泛的发病率和死亡率。这是艾滋病的一个特殊问题。 这可能是HIV致病的一个辅助因素。更好的 人巨细胞病毒DNA复制及其分子机制的研究进展 需要监管来帮助制定抗病毒战略。裂解相 DNA复制既需要基因定义的顺式作用复制子， OriLyt和反式作用因子，如病毒特异的DNA聚合酶。 先前的研究导致了巨细胞病毒机制的模型的发展 在这个模型中，转录本有助于组装 通过促进oriLyt内部的链分离而形成的预引发复合体。 这项建议的具体目的是：1)更好地建立 使用标准的oriLyt序列中基本元件的结构 分子遗传学方法；2)确定顺式作用元件 参与调节oriLyt转录本的表达，并鉴定其 同源激活剂；3)测试申请人S启动者成绩单模型 4)检测IE2/oriLyt的作用 复制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.