STRUCTURAL STUDIES OF NUCLEOTIDE EXCISION REPAIR ENZYMES

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 在各种DNA修复机制中，核苷酸切除修复(NER)的独特之处在于它能够处理广泛的结构无关DNA损伤。在细菌中，NER的初始步骤由三种蛋白质执行：UvrA、UvrB和UvrC。UvrA+UvrB复合体监测DNA并识别损伤。在遇到损伤后，UvrA从复合体中解离，使UvrB与受损的DNA结合。UvrB+DNA切开前复合体的损伤搜索和形成受ATP调控。UvrB随后与UvrC和其他因子合作，恢复原始DNA序列。我们项目的总体目标是实现对细菌NER蛋白损伤识别和修复的分子理解。具体地说，我们正在进行结构研究，以深入了解UvrA和UvrB如何合作识别大量结构多样化的DNA损伤，以及UvrB+DNA复合体如何呈现受损的DNA进行切割和额外处理。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Among the various DNA repair mechanisms, nucleotide excision repair (NER) is unique in its ability to process a wide range of structurally unrelated DNA lesions. In bacteria, the initial steps of NER are performed by three proteins: UvrA, UvrB, and UvrC. The UvrA+UvrB complex monitors DNA and recognizes damage. After the lesion is encountered, UvrA dissociates from the complex and leaves UvrB bound to the damaged DNA. Damage searching and formation of the UvrB+DNA pre-incision complex are regulated by ATP. UvrB subsequently cooperates with UvrC and other factors to restore the original DNA sequence. The overall goal of our project is to achieve a molecular understanding of damage recognition and repair by bacterial NER proteins. Specifically, we are performing structural studies to gain insights into how UvrA and UvrB can cooperate to recognize a large number of structurally diverse DNA lesions, and how UvrB+DNA complex presents the damaged DNA for cleavage and additional processing.