3D architecture of DNA Pol α reveals the functional core of multi-subunit replicative polymerases

Sebastian Klinge, Rafael Núñez-Ramírez, Oscar Llorca, Luca Pellegrini
2009 EMBO Journal  
Eukaryotic DNA replication requires the coordinated activity of the multi-subunit DNA polymerases: Pol a, Pol d and Pol e. 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 a. The crystal structure of the C-terminal domain (CTD) of the
more » ... alytic subunit bound to the B subunit illustrates a conserved mechanism of accessory factor recruitment by replicative polymerases. The EM reconstructions of Pol a 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.
doi:10.1038/emboj.2009.150 pmid:19494830 pmcid:PMC2693882 fatcat:ceajamd6g5hwnenlrk2rwymcu4