ROLE OF GENE UVSW IN ERROR-PRONE REPAIR BY BACTERIOPHAGE T4

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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 mutations of uvsW has been engineered, providing a rigorously defined null allele. The expression and regulation of uvsW is being explored by a combination of DNA-sequencing, northern-blot, primer-runoff and RNA-sequencing methods.