Fig. 4: A conserved mechanism for regulating replisome disassembly in eukaryotes.

a, Comparison of cryo-EM density maps for human replisome complexes (CMG, TIMELESS, TIPIN, CLASPIN, AND-1 and Pol-ε) bound to DNA substrates either lacking (left) or featuring (right; EMDB: EMD-13375 (ref. ²⁸)) a 15-nucleotide 5ʹ flap, representing the excluded DNA strand. Density is coloured according to chain occupancy using a radius of 5 Å, with the excluded strand coloured manually in UCSF Chimera. ssDNA, single-stranded DNA. b, Alternative views of the ZnF domains of MCM3 and MCM5 during replication elongation (red box, excluded strand present²⁸) and termination (green box, excluded strand absent). In the upper panel of the red box, the dashed line shows a putative path for the excluded ssDNA beyond the density observed in a, right. In the lower panel of the red box, four sugar-phosphate backbone linkages were built into the excluded strand density (see a, right; EMDB: EMD-13375 (ref. ²⁸)). H. sapiens, Homo sapiens. c, Model for the regulation of CMG ubiquitylation. LRR-interacting regions of MCM are occluded in the MCM double hexamer (see Extended Data Fig. 11a) and by the excluded DNA strand at replication forks (see a, b) (red box). Loss of the excluded strand upon termination allows LRR–MCM engagement, CMG ubiquitylation and replisome disassembly (green box).