3D architecture of DNA Pol alpha reveals the functional core of multi-subunit replicative polymerases.
Eukaryotic DNA replication requires the coordinated activity of the multi-subunit DNA polymerases: Pol alpha, Pol delta and Pol epsilon. The conserved catalytic and regulatory B subunits associate in a constitutive heterodimer that represents the functional core of all three replicative polymerases. Here, we combine X-ray crystallography and electron microscopy (EM) ... to describe subunit interaction and 3D architecture of heterodimeric yeast Pol alpha. The crystal structure of the C-terminal domain (CTD) of the catalytic subunit bound to the B subunit illustrates a conserved mechanism of accessory factor recruitment by replicative polymerases. The EM reconstructions of Pol alpha reveal a bilobal shape with separate catalytic and regulatory modules. Docking of the B-CTD complex in the EM reconstruction shows that the B subunit is tethered to the polymerase domain through a structured but flexible linker. Our combined findings provide a structural template for the common functional architecture of the three major replicative DNA polymerases.
Mesh Terms:
Amino Acid Sequence, Animals, Crystallography, X-Ray, DNA Polymerase I, Escherichia coli, Humans, Microscopy, Electron, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Tertiary, Protein Subunits, Saccharomyces cerevisiae, Sequence Alignment
Amino Acid Sequence, Animals, Crystallography, X-Ray, DNA Polymerase I, Escherichia coli, Humans, Microscopy, Electron, Models, Molecular, Molecular Sequence Data, Protein Conformation, Protein Structure, Tertiary, Protein Subunits, Saccharomyces cerevisiae, Sequence Alignment
EMBO J.
Date: Jul. 08, 2009
PubMed ID: 19494830
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