Two dNTP triphosphohydrolases from Pseudomonas aeruginosa possess diverse substrate

The dNTPs act as substrates for DNA replication.The intracellular concentration of each dNTP must bestrictly controlled, because an imbalance of dNTPscan result in mutations caused by replication errors[1,2]. The de novo synthesis of the four dNTPs occursthrough either reduction of NDPs by ribonucleotidereductase or a salvage pathway involving phosphory-lation of the corresponding deoxyribonucleosideswhen they are available [3,4]. The activities of the keyenzymes in both the de novo and salvage pathwaysare subject to complex allosteric control mechanisms[5]. Enzymes involved in the degradation of dNTPsalso participate in the regulation of the dNTP pool.Substrate cycling between deoxyribonucleosides andthe corresponding monophosphates is thought to beintegral to the regulation of the pool size of dNTPs[6].Most dNTP-hydrolyzing enzymes that have beencharacterized recognize noncanonical dNTPs such as8-oxo-dGTP, dUTP, dITP, and 2-oxo-dATP [7].