The Mcm2-7 motor unwinds DNA using an approach distinct from that of superfamily III helicases, and accesses multiple ring configurations and assembly states during the initiation of DNA replication.

The CMG complex, the replicative helicase in eukaryotes, uses a different mechanism from bacterial and viral helicases by engaging both strands of parental DNA with substantial force and unwinding the duplex within the central channel of CMG.

Ubiquitylation of the CMG helicase is inhibited throughout the initiation and elongation phases of chromosome replication by the DNA structure of a replication fork.

Biochemical data demonstrate an unexpected and critical function for the enigmatic Mcm10 protein in helping the eukaryotic CMG helicase/replisome bypass roadblocks on the DNA that may also explain Mcm10 function at origins of replication.

Eukaryotic replisomes are strongly connected together to replicate both sister DNAs produced from a bidirectional origin.

CMG helicase translocates with force while encircling duplex DNA, enabling two opposing CMG complexes at an origin to melt the duplex and switch to encircling separate single strands.

A multi-step process of helicase activation sensitizes replication initiation to the extent of replicative helicase phosphorylation.

UBX proteins reduce the ubiquitin threshold of mammalian p97-UFD1-NPL4.

Nucleosomal DNAs assembled or modified by different chromatin remodeling enzymes differentially impact the origin licensing and helicase activation steps of replication initiation.

Analysis of an essential motif in Mcm4 provides insights into replicative helicase double-hexamer formation and the first step requiring this intermediate during replication initiation.