Abstract
DNA polymerase δ (Pol δ) is a high-fidelity polymerase that has a central role in replication from yeast to humans. We present the crystal structure of the catalytic subunit of yeast Pol δ in ternary complex with a template primer and an incoming nucleotide. The structure, determined at 2.0-Å resolution, catches the enzyme in the act of replication, revealing how the polymerase and exonuclease domains are juxtaposed relative to each other and how a correct nucleotide is selected and incorporated. The structure also reveals the 'sensing' interactions near the primer terminus, which signal a switch from the polymerizing to the editing mode. Taken together, the structure provides a chemical basis for the bulk of DNA synthesis in eukaryotic cells and a framework for understanding the effects of cancer-causing mutations in Pol δ.
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Acknowledgements
We thank the staff at Brookhaven National Laboratory and the Advanced Photon Source for facilitating X-ray data collection. This work was supported by grant CA138546 from the US National Institutes of Health.
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M.K.S. and R.E.J. performed the experiments; all of the authors contributed to the concepts and to the writing of the paper.
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Swan, M., Johnson, R., Prakash, L. et al. Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase δ. Nat Struct Mol Biol 16, 979–986 (2009). https://doi.org/10.1038/nsmb.1663
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DOI: https://doi.org/10.1038/nsmb.1663
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