Abstract
Epigenetic inheritance requires the transfer of parental histones to newly synthesized DNA during eukaryotic chromosome replication, yet the structural mechanisms underlying replisome engagement with nucleosomes remain unclear. Here we establish an in vitro chromatin replication system and report four cryo-EM structures of the human replisome in complex with a parental nucleosome. The structures capture distinct states of nucleosomal DNA unwrapping and nucleosome integrity during nucleosome disassembly by the encroaching replisome.