The Structure of T. aquaticus DNA Polymerase III Is Distinct from Eukaryotic Replicative DNA Polymerases

SummaryThe crystal structure of Thermus aquaticus DNA polymerase III α subunit reveals that the structure of the catalytic domain of the eubacterial replicative polymerase is unrelated to that of the eukaryotic replicative polymerase but rather belongs to the Polβ-like nucleotidyltransferase superfamily. A model of the polymerase complexed with both DNA and β-sliding clamp interacting with a reoriented binding domain and internal β binding site was constructed that is consistent with existing biochemical data. Within the crystal, two C-terminal domains are interacting through a surface that is larger than many dimer interfaces. Since replicative polymerases of eubacteria and eukaryotes/archaea are not homologous, the nature of the replicative polymerase in the last common ancestor is unknown. Although other possibilities have been proposed, the plausibility of a ribozyme DNA polymerase should be considered.