Structural biology

Two major projects currently on going are: (1) Structure determination of one of the most common human oncogene products, ras oncogene products (p21 proteins); and (2) Structure determination of DNA damaged by a mutagen and UV radiation using NMR and x-ray crystallography. There is compelling evidence that human cancer develops as a consequence of genetic changes (probably multiple) is some members of a selected set of cellular genes. DNA isolated from a variety of tumors, but not normal tissues, possesses the ability to malignantly transform non-tumorigenic cells. Subsequently, many oncogenes responsible for such transformation have been isolated from human tumors and cell lines, and spontaneous, virus, chemical, or radiation-induced animal tumors. We have utilized two-dimensional NMR spectroscopy to analyze experimentally the solution structure of a self-complementary DNA octanucleotide, d-GGGTACCC, cross-linked with psoralen. This DNA contains a central 5'-TpA sequence which has been shown to be highly reactive with psoralens