STRUCTURAL STUDIES OF NUCLEOTIDE EXCISION REPAIR ENZYMES

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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.