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

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


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalytic Domain
  • Crystallography, X-Ray
  • DNA / biosynthesis*
  • DNA / chemistry*
  • DNA Polymerase III / chemistry*
  • DNA Polymerase III / genetics
  • DNA Polymerase III / metabolism
  • Humans
  • Mice
  • Models, Molecular
  • Mutation
  • Neoplasms / enzymology
  • Neoplasms / genetics
  • Nucleic Acid Conformation
  • Protein Structure, Quaternary
  • Protein Structure, Tertiary
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / chemistry*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism


  • POL3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • DNA
  • DNA Polymerase III

Associated data

  • PDB/3IAY