T4 Phage dNTP Synthetase, a Multienzyme Complex for Dexyribonucleotide

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The long-range goals of this research are (1) to understand how DNA precursor biosynthesis is regulated; (2) to understand how regulatory mechanisms affecting DNA precursor synthesis control the rate and fidelity of DNA replication; (3) to understand the metabolic and genetic consequences of pertubations in DNA precursor biosynthesis; and (4) to contribute toward an understanding of mechanisms of action of the enzymes involved. The proposed research involves a multienzyme complex, formed in T4 phage- infected Escherichia coli, which carries out the synthesis of deoxyribonucleoside triphosphates (dNTPs). This is the T4 dNTP synthetase complex. The wealth of genetic and biochemical knowledge of T4 permits a variety of powerful approaches to understanding protein-protein interactions in this system. %%% DNA replication uses precursors, the deoxyribonucleoside triphosphates, which are specialized for that purpose and for little else. In addition to replication, dNTPs are used in DNA repair and in recombination; also, bacteria used dTTP in cell wall synthesis. This limited repertoire of metabolic role makes it possible for DNA synthesis to be regulated specifically at the level of precursor formation. This research attempts to describe how dNTP synthesis is controlled and the extend to which these mechanisms contribute toward the control of DNA replication.