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Structural biology

A mechanism for all polymerases

Nature volume 391, pages 231–232 (1998)Cite this article

Possibly the earliest enzymatic activity to appear in evolution was that of the polynucleotide polymerases — the ability to replicate the genome accurately being a prerequisite for evolution itself. Thus, one might anticipate that the mechanism by which polymerases work would be both simple and universal. Further, these enzymatic scribes must faithfully copy the sequences of the genome into daughter nucleic acid, or the information contained within will be lost for ever. Finally, replicative DNA polymerases are highly processive, traversing the whole genome of a virus DNA without falling off.

On pages 251 and 304 of this issue, Doublié et al.1 and Kiefer et al.2 provide significant insights into the catalytic mechanism, fidelity and processivity of DNA polymerases. In a detailed crystal structure at 2.2 Å resolution, Doublié et al. have captured the DNA polymerase that replicates bacteriophage T7 DNA, along with the Escherichia coli thioredoxin in the act of adding a deoxynucleoside triphosphate (dNTP) to a primer-template DNA. The incoming dNTP (actually dideoxy here) is accompanied by two magnesium ions, which are bound to the phosphates of the nucleotide and to two aspartic-acid residues that are widely conserved among DNA and RNA polymerases. To prevent the reaction from occurring in the crystal, the authors used a dideoxynucleotide at the primer terminus whose 3′ OH, when present, would interact with one of the two metal ions.

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Figure 1: The two-metal-ion mechanism of polynucleotide polymerases3 in the context of the T7 DNA po.

T. ELLENBERGER

Figure 2: Structure of the T7 DNA polymerase, solved by Doublié et al.1, locked in synthesis mode.

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  1. the Department of Molecular Biophysics and Biochemistry, and the Howard Hughes Medical Institute, Yale University, 266 Whitney Avenue, New Haven, 06520-8114, Connecticut, USA

    Thomas A. Steitz

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Steitz, T. A mechanism for all polymerases. Nature 391, 231–232 (1998). https://doi.org/10.1038/34542

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