There are many ways to control the biological activity of proteins, e.g., activation or inhibition of their synthesis at the transcriptional or translational level, specific modifications, or destruction of the proteins. The destruction, or degradation, of proteins by proteases is complete and irreversible and is known to be an essential regulatory mechanism vital for biological processes and diseases ranging from cancer to DNA repair. While the majority of cellular proteins are stable, there are a small percentage of cellular proteins that are unstable and these proteins are usually temporally expressed and act in a regulatory manner. Understanding the mechanisms by which proteases selectively recognize and degrade these unstable proteins is important in determining how they act in a temporal fashion to regulate biological processes.
We study the Escherichia coli UmuD’ (UmuD) and UmuC proteins which comprise an error-prone DNA polymerase necessary for the survival of the bacterium following extensive DNA damage via the process known as translesion DNA synthesis. Ironically, this DNA polymerase demonstrates low fidelity resulting in mutations in the bacterial DNA. This is a compromise allowing the bacterium to survive at the expense of fidelity. Following completion of all translesion DNA synthesis UmuD’ (UmuD) and UmuC are no longer required and are inactivated by the action of various E. coli proteases. The research in my laboratory involves the use of bacterial genetics, molecular biology, and biochemistry to elucidate the interaction of these regulatory proteins with the cellular proteases involved in their selective degradation.
