The objective of this current research is to investigate the mechanisms of mutagenesis and DNA repair induced by the nitrated pyrenes. To accomplish this goal, his laboratory has used the tools of organic synthesis and recombinant DNA technology to construct specific DNA fragments and viral genomes that contained, at pre-selected sites, the major DNA adduct formed by 1-nitropyrene. This technology will be further employed to construct specific mutagenic hot-spot sequences in DNA. Sequence-specificity of mutagenesis will be investigated by introducing these modified viral genomes in Escherichia coli cells,, where the DNA replication and repair systems will act upon the single DNA adduct. A primary goal of this work is to define the relationship between the structure and three-dimensional effects of a lesion in DNA and the mutagenicity and DNA repair that it may induce. Another important aim is to understand the mechanism of how the repair proteins protect cells against the toxic and mutagenic properties of these DNA damaging agents.
