Structural basis of high-fidelity DNA synthesis by yeast DNA polymerase delta.
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.
Swan
Michael K
MK
Department of Structural & Chemical Biology, Mount Sinai School of Medicine, New York, New York, USA.
Johnson
Robert E
RE
Prakash
Louise
L
Prakash
Satya
S
Aggarwal
Aneel K
AK
D000595:Amino Acid Sequence; D000818:Animals; D020134:Catalytic Domain; D018360:Crystallography, X-Ray; D004247:DNA / Q000096:biosynthesis* / Q000737:chemistry*; D004258:DNA Polymerase III / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009154:Mutation; D009369:Neoplasms / Q000201:enzymology / Q000235:genetics; D009690:Nucleic Acid Conformation; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
C491232:POL3 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; D004258:DNA Polymerase III