Extended Data Fig. 2: Structure details of the Pol ε ternary complex with PCNA.

(a). Cryo-EM density (shown as a mesh) around the iron-sulphur cluster (4Fe–4S) that is coordinated at the Pol ε CysX motif near the junction of P and Palm domains. (b) Two views of the polymerase active site of Pol ε in the open conformation. The incoming ddATP nucleotide and coordinating side chain residues are shown as sticks. (c) Comparison of the Thumb domains of Pol ε (left) and Pol δ (ref. ¹³) (right). The unique insert in Pol ε and the corresponding location in Pol δ are marked in light blue. The absence of this insert in Pol δ allows the PIP-box to interact with the PCNA protomer underneath the Thumb domain. (d) Focused view on the contact site between the Pol ε P domain and the closest PCNA protomer (left). PCNA residues R210 and Y211 are shown as sticks. The dashed line indicates the electrostatic interaction formed between R210 and the DNA substrate. The conformation that these two side chains adopt in the other two PCNA protomers near adjacent to Thumb and PIP-box, respectively, are shown in the middle and right panels. (e–g) Ribbon models of Pol ε (e) and Pol δ (f, g)¹³ in complex with PCNA, aligned by their catalytic domains. (h) Close−up view on the β-hairpin of the exonuclease domain (dark orange) for Pol ε (left) and Pol δ (ref. ¹³) (right).