Comparative structural analysis, interactions with target proteins, and protein engineering are used to elucidate the factors controlling calcium-induced activation of CaBPs, and the coupling of structure and function in this protein family. Structure determination of novel CaBPs is providing new information on links between calcium and phosphorylation signaling pathways. The recognition and functional roles of non-regular DNA structures in genetic replication, recombination and repair is a second major area of research. The main emphasis in the laboratory is elucidating the structural basis for the role of replication protein A in orchestrating the processing of damaged DNA by DNA repair enzymes. In related research, we seek a fundamental understanding of the binding and reactivity of anticancer agents that create DNA lesions not efficiently processed by the cellular DNA repair machinery.
Current effort is focused on mechanisms for in-situ activation of DNA alkylating agents.
Publications G. Mer, A. Bochkarev, R. Gupta, E. Bochkarev, L.D. Frappier, C.J. Ingles, A.M. Edwards and W.J. Chazin. N.J. Skelton and W.J. Chazin. Solution structure determination of proteins using NMR spectroscopy. M. Nelson and W.J. Chazin. J. Smith, L.G. Paloma, D.A. Case and W.J. Chazin.