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

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.

SUBMITTER: Swan MK

PROVIDER: S-EPMC3055789 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

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

Swan Michael K MK Johnson Robert E RE Prakash Louise L Prakash Satya S Aggarwal Aneel K AK

Nature structural & molecular biology 20090830 9

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 ...[more]

PMID: 19718023

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