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Nat Struct Mol Biol. 2009 Sep;16(9):979-86. doi: 10.1038/nsmb.1663. Epub 2009 Aug 30.

Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta.

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Department of Structural & Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA.


DNA polymerase delta (Pol delta) 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 delta in ternary complex with a template primer and an incoming nucleotide. The structure, determined at 2.0-A 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 delta.

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