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

Journal Article · · Nat. Struct. Mol. Biol.
DOI:https://doi.org/10.1038/nsmb.1663· OSTI ID:1005867

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-{angstrom} 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}.

Research Organization:
Argonne National Laboratory (ANL)
Sponsoring Organization:
USDOE
OSTI ID:
1005867
Journal Information:
Nat. Struct. Mol. Biol., Journal Name: Nat. Struct. Mol. Biol. Journal Issue: (9) ; 09, 2009 Vol. 16; ISSN 1545-9993
Country of Publication:
United States
Language:
ENGLISH

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