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Solution structure of a viral DNA repair polymerase

Abstract

DNA polymerase X (Pol X) from the African swine fever virus (ASFV) specifically binds intermediates in the single-nucleotide base-excision repair process, an activity indicative of repair function. In addition, Pol X catalyzes DNA polymerization with low nucleotide-insertion fidelity. The structural mechanisms by which DNA polymerases confer high or low fidelity in DNA polymerization remain to be elucidated. The three-dimensional structure of Pol X has been determined. Unlike other DNA polymerases, Pol X is formed from only a palm and a C-terminal subdomain. Pol X has a novel palm subdomain fold, containing a positively charged helix at the DNA binding surface. Purine deoxynucleoside triphosphate (dNTP) substrates bind between the palm and C-terminal subdomain, at a dNTP-binding helix, and induce a unique conformation in Pol X. The purine dNTP–bound conformation and high binding affinity for dGTP–Mg2+ of Pol X may contribute to its low fidelity.

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Figure 1: The Pol X family and the NMR solution structure of ASFV Pol X.
Figure 2: Pol X binding to intermediates in base-excision repair and mapping of the DNA binding surface.
Figure 3: Interaction of dNTP–Mg2+ substrates with Pol X as determined by NMR.
Figure 4: Chemical shift mapping and fluorescence binding studies of dNTP–Mg2+ interaction with Pol X.

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Acknowledgements

This research was supported by grants from the National Institutes of Health.

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Correspondence to Gregory P. Mullen.

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Maciejewski, M., Shin, R., Pan, B. et al. Solution structure of a viral DNA repair polymerase. Nat Struct Mol Biol 8, 936–941 (2001). https://doi.org/10.1038/nsb1101-936

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