Extended Data Fig. 6: Compatibility of PCNA binding to Pol ε cat with other interactors of Pol ε.

(a, b) Pseudo-atomic models of the core human replisome (PDB: 7PFO, Jones 2021³⁶) with the subcomplex of Pol ε cat-PCNA in two possible configurations. Pol ε cat-PCNA was placed either (a) based on the cryo-EM structure of the S. cerevisiae Pol ε holoenzyme (PDB: 6WJV, Yuan 2020³⁵) or (b) based on reported cryo-EM density adjacent to the MCM channel exit in a structure containing S. cerevisiae CMG and Pol ε⁵³. (c) Detailed view of the pseudo-atomic model composed of the S. cerevisiae Pol ε holoenzyme (PDB: 6WJV, Yuan 2020³⁵) and the PCNA interaction of the human ternary complex that we report here. Recruitment of PCNA is sterically compatible with the rigid conformation of Pol ε. (d) The interaction of the Pol ε ternary complex with PCNA is sterically compatible the recruitment of the Ctf18-1-8 module of the Ctf18-RFC clamp loader (PDB: 6S2F, Stokes 2020⁵⁴).