Mutagens contribute to the human burden of heritable birth defects and cancer and probably to heart disease as well. Most mutagens in most organisms act by triggering a process called error-prone repair (EPR). Such mutagens' primary action is to damage DNA in ways that block the progress of the DNA replication complex. EPR then facilitates damage bypass in a poorly templated (and therefore mutagenic) manner. uvsW is a crucial but mysterious gene in the bacteriophage T4 EPR system. Mutations in uvsW depress recombination, increase killing and abolish mutagenesis by agents acting through EPR. Temperature-sensitive mutations of uvsW have been generated and characterized by mapping and complementation tests and their effects on survival, recombination and mutagenesis have been determined. A deletion mutation of uvsW has been engineered, providing a rigorously defined null allele. This work is now in press and the project is completed.
