3D architecture of DNA Pol α reveals the functional core of multi-subunit replicative polymerases
Open Access
- 4 June 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 28 (13), 1978-1987
- https://doi.org/10.1038/emboj.2009.150
Abstract
Eukaryotic DNA replication requires the coordinated activity of the multi‐subunit DNA polymerases: Pol α, Pol δ and Pol ε. 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 α. 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 α 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.Keywords
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