We seek to learn about the mechanism(s) regulating the activity of potentially mutagenic DNA polymerases.
We would like to elucidate the mechanism(s) that regulate the activity of the evolutionary conserved and potentially mutagenic specialized Y family of DNA polymerases in Escherichia coli. The research focuses on understanding the formation of a multi-protein complex (MPC) in vivo and in vitro that is known to regulate the activity of one of these DNA polymerases. MPC formation is likely to regulate the activity of not only one but both error-prone DNA polymerases, permitting both survival in otherwise lethal conditions and modulation of the cell’s mutagenic outcome.
Due to the evolutionary conservation of most of the proteins involved in the MPC, the research has far reaching implications; it will provide insights not only to the organization of these proteins in other organisms, but also to their function in mutagenesis. This knowledge can in turn promote innovative approaches to counter the development of resistance to antibiotics in bacteria or cancer in humans.