Fig. 2: Cryo-EM density and model of selected regions of the Pol δ–DNA–PCNA complex.

a Map regions showing the critical interactions tethering the polymerase to PCNA. Models are colored by domain. Inset 1: main-chain hydrogen bonds between the CTD of p125 and the IDCL of PCNA, indicated as red dotted lines. Residues involved in the interactions are labeled and colored by domain. Amino acid side chains are not shown. Inset 2: interaction between the p125 PIP-box and PCNA. b Sequence alignment of the CTD of human and Saccharomyches cerevisiae Pol δ and motifs. Asterisks correspond to conserved residues. Conserved cysteines in CysA and CysB motifs are highlighted in magenta. c Map region and model of the CTD of p125. Interfacial residues are boxed and colored by domain. Residues participating in polar interactions are connected by double-headed arrows. Some of the amino acid side chains are omitted for clarity. d Model region showing the pocket between the p125 and p50 subunits, where the CTD is inserted. p125 and p50 domains are shown as surfaces, and the CTD as a ribbon. The FeS cofactor and zinc ion in the CTD are shown as spheres. The p12 subunit was removed for clarity. e Map region and model of the p12 subunit of Pol δ, and p12 amino acid sequence and motifs. The segment of the p12 sequence that was modelled is boxed. Interfacial residues are boxed and colored by domain. Residues participating in polar interactions are connected by double-head arrows. f Model region showing the position of p12 relative to the holoenzyme. p12 and CTD are shown as ribbons and the latter is shown with enhanced transparency. p125 and p50 domains are shown as surfaces. g Model of human Pol δ in ribbon representation, showing the p12 subunit connecting the catalytic and regulatory modules.