CHARACTERIZATION OF NEW MUTANTS: We will continue to map and characterize our library of new ionizing radiation-sensitive mutants of Escherichia coli K-12. DNA REPAIR STUDIES: We will determine the molecular basis and genetic control of a new inducible recovery phenomenon in E. coli that shows a specificity for ionizing radiation-produced DNA damage. We call this process Medium Dependent Resistance (MDR). Current genetic evidence indicates that MDR is composed of several different repair systems. We will follow-up our preliminary experiments that show that MDR enhances the ability of cells to repair both DNA single- and double-strand breaks, and we also plan to study the roles of repair replication and postreplication repair in MDR after ionizing irradiation. We will then attempt to associate the multiple genetic pathways of resistance to ionizing radiation with specific molecular repair functions. CLONING OF NEW GENES: We plan to clone and identify the products of some of our newly discovered genes that affect ionizing radiation sensitivity. HEALTH RELATEDNESS: Error-prone DNA repair appears to be the molecular basis for radiation mutagenesis. Since mutagenesis may be the first step toward carcinogenesis, a better understanding of the molecular mechanisms for DNA repair and mutagenesis should provide a better understanding of the molecular basis of carcinogenesis.
