One aspect of our work focuses on molecular mechanisms that affect the fidelity of DNA replication and repair. The other problem of interest is genetic recombination and how it contributes to repair of damage. Our most recent work on mutagenesis focuses on the fascinating but difficult problem of deletion mutagenesis. Deletion mutagenesis contributes to cancer onset by altering or disrupting genes important to regulation of normal cellular growth patterns. Deletion formation is especially important to understanding the molecular basis of cancer since inactivation of tumor suppressor genes such as the retinoblastoma gene often results from deletion.
Deletions are genetically devastating because of their permanence.
Unlike a point mutation, deletions can not be reverted. But deletions are relatively rare, often occurring at a rate of only 10-6 deletions per cell division. Thus, the problem in studying the biochemistry of deletions is a very low signal to noise ratio. To address this problem we needed a system with well defined genetics, a rapid rate of DNA replication, and the potential for easy biochemical manipulation. Bacteriophage T7 provides such a system.