STRUCTURAL STUDIES OF NUCLEOTIDE EXCISION REPAIR ENZYMES

这个子项目是利用资源的许多研究子项目之一。 由NIH/NCRR资助的中心拨款提供。对子项目的主要支持 子项目的首席调查员可能是由其他来源提供的， 包括美国国立卫生研究院的其他来源。为子项目列出的总成本可能 表示该子项目使用的中心基础设施的估计数量， 不是由NCRR赠款提供给次级项目或次级项目工作人员的直接资金。 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的调控。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. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. 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 preincision 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.