Reference: Swan MK, et al. (2009) Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta. Nat Struct Mol Biol 16(9):979-86

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Abstract


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.

Reference Type
Journal Article | Research Support, N.I.H., Extramural
Authors
Swan MK, Johnson RE, Prakash L, Prakash S, Aggarwal AK
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