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 and is expressed in small amounts at an unusual time during phage development. Mutations in uvsW depress recombination, increase killing and abolish mutagenesis by agents acting through EPR. Temperature-sensitive mutations of uvsW have now been generated and characterized by mapping and complimentation tests and their effects on survival and mutagenesis are being determined. A plasmid bearing and uvsW region has been constructed and a deletion mutation thereof reintroduced into the T4 chromosome. This mutation will provide a rigorously defined null allele. It and other uvsW mutations will be used to determine the basis of the increased hydroxyurea sensitivity which is diagnostic of uvsW mutations. The wild-type uvsW gene will be placed on a plasmid under conditions suitable for overproduction of the gene product, whose properties will then be examined.