Enzymatic Mechanism of Herpes Virus DNA Replication

超出所提供的空间。本研究的目的是了解（i）疱疹病毒DNA复制的启动机制，（ii）疱疹病毒DNA复制过程中发生的倒位机制和（iii）影响疱疹病毒感染神经细胞中病毒潜伏期发展的因素。我们预计，这些研究将为我们提供一个深入了解复制，重组和潜伏期的一类重要的人类病原体。调查将按以下方式沿着进行。A.通过细胞hTid-1 DnaJ分子伴侣刺激多聚体起点结合蛋白（UL 9蛋白）与HSV-1 DNA复制起点Oris结合的分析。B。神经F盒蛋白（NFB 42）在HSV- 1潜伏期中的作用 1.结合NFB 42后UL 9蛋白的泛素化和降解。 2.研究UL 9蛋白与NFB 42相互作用的磷酸化状态。C.核酸内切酶G在HSV- 1基因组序列倒位起始中的作用。 1.核酸内切酶G切割一个序列的研究。 2. HSV- 1感染对核酸内切酶G水平的影响。 3. HSV-1感染前后核酸内切酶G的细胞定位4.核酸内切酶G与其他蛋白质的相互作用。 5.核酸内切酶G的抑制对α-序列介导的重组的影响。性能现场=

EXCEED THE SPACE PROVIDED. The aim of this research is to understand (i) the mechanism of initiation of herpes virus DNA replication, (ii) the mechanism of inversion that occurs during herpes virus DNA replication and (iii) the factors that influence the development of viral latency in herpes virus-infected neuronal cells. We anticipate that these studies will provide us with an insight into the replication, recombination and latency of a significant class of human pathogens. The investigation will be organized along the following lines. A. Analysis of the stimulation of binding of multimeric origin binding protein (UL9 protein) to Oris, an origin of HSV-1 DNA replication, by the cellular hTid-1 DnaJ chaperone. B. Role of neural F box protein (NFB42) in HSV- 1 latency. 1. Ubiquitination and degradation of UL9 protein upon binding NFB42. 2. Investigation of state of phosphorylation of UL9 protein on its interaction with NFB42. C. Role of endonuclease G in the initiation of sequence inversion in the HSV- 1 genome. 1. Studies of a sequence cleavage by endonuclease G. 2. Effect of HSV- 1 infection on levels of endonuclease G. 3. Cellular localization of endonuclease G pre- and post HSV-1 infection 4. Interaction of endonuclease G with other proteins. 5. Effect of suppression of endonuclease G on a-sequence-mediated recombination. PERFORMANCE SITE ========================================Section End===========================================