ERROR-PRONE REPAIR IN 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 mutagans, 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 there fore mutagenic) manner. Thus, the DNA polymerase is expected to play a crucial role in EPR. We have recently found that certain mutations of the bacteriophage T4 DNA polymerase gene can enhance or suppress EPR. The strongest enhancing mutation, hm (for hypermutable), also changes the specificity of EPR, preferentially increasing the frequency of base pair substitution mutations. Although hm has been difficult to map by conventional crosses, we have now assigned it to the DNA polymerase gene. We have also ascertained the effect on EPR of some previously described DNA polymerase mutations, one of which virtually abolishes EPR. Thus, the T4 DNA polymerase is a major determinant of the quantity and quality of EPR.