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

Michael K. Swan, Robert E. Johnson, Louise Prakash, Satya Prakash, Aneel K. Aggarwal

Research output: Contribution to journalArticle

152 Citations (Scopus)

Abstract

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

Original languageEnglish (US)
Pages (from-to)979-986
Number of pages8
JournalNature Structural and Molecular Biology
Volume16
Issue number9
DOIs
StatePublished - Sep 2009

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DNA-Directed DNA Polymerase
Nucleotides
Yeasts
Exonucleases
DNA
Eukaryotic Cells
Catalytic Domain
Mutation
Enzymes
Neoplasms

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase Δ. / Swan, Michael K.; Johnson, Robert E.; Prakash, Louise; Prakash, Satya; Aggarwal, Aneel K.

In: Nature Structural and Molecular Biology, Vol. 16, No. 9, 09.2009, p. 979-986.

Research output: Contribution to journalArticle

Swan, Michael K. ; Johnson, Robert E. ; Prakash, Louise ; Prakash, Satya ; Aggarwal, Aneel K. / Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase Δ. In: Nature Structural and Molecular Biology. 2009 ; Vol. 16, No. 9. pp. 979-986.
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