Detailed information is available regarding the mechanisms of regulating specific genes in bacteria. Much less is known about how these individual control systems interact so as to coordinate the functions of multigene systems. We propose to genetically approach control of several multigene systems and how they might interact. We will work on 1) the histidine operon and how it interacts with the related purine pathway and the cells control of cell division, 2) the purine pathway per se will be investigated to determine how the many genes in its separate branches are controlled, 3) a new system of gene regulation will be investigated which we believe is related to purine metabolism and involves structural alteration of DNA. The system seems to cause reversible inactivation of cryptic prophages, 4) the NAD pathway involves not only biosynthesis but also recycling pathway for salvage of pyridine nucleotides. This system is involved in DNA repair as well as oxidation/reduction reactions. The control of this complex pathway and its integration with cellular regulatory mechanisms will be pursued. All of these endeavors will involve a heavily genetic approach employing transposable elements, some of which form operon fusions of the lac operon to the promoter of the target gene. Many of the methods used are one developed in this lab.
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