Fig. 4. Atomic model of the leading strand replisome.

a 2D class averages of cryo-EM images of purified native Pol ε in complex with recombinant CMG. b A 3-kb forked DNA, primed with a 5′-³²P-DNA oligonucleotide, is replicated in the presence of CMG, RPA, PCNA, and RFC, using either Pol ε holoenzyme (lane 1), catalytic Pol2 NTD (lane 2), or catalytic Pol2 NTD plus Pol2 CTD (lane 3). Lanes 4–6 are the same as lanes 1–3, except in the absence of PCNA and RFC. c A model showing how the CMG helicase is coupled with the holoenzyme Pol ε in which the Dpb2 OB domain likely bridges the leading strand DNA path from CMG to the Pol ε catalytic entry. The leading strand path is drawn as an orange dashed line with two arrowheads indicating the ssDNA moving direction.