Jacob Peter Matson, Raluca Dumitru ... Jeanette Gowen Cook
The unique cell cycle variations of pluripotent stem cells ensures that the first step in DNA replication is particularly fast and this rapid rate, in turn, restrains early differentiation.
Nucleosomal DNAs assembled or modified by different chromatin remodeling enzymes differentially impact the origin licensing and helicase activation steps of replication initiation.
Human cells that lack a subunit in their origin recognition complex are viable, which suggests the existence of alternative mechanisms to initiate DNA replication.
The ~20,000 origins of replication in human cell lines that are reproducibly identified by multiple techniques in multiple cell lines are distant from known origin recognition complex and MCM2-7-binding sites.
Franziska Bleichert, Maxim Balasov ... James M Berger
Electron microscopy uncovers the structure of the origin recognition complex (ORC) in metazoans, and reveals how mutations in the ORC6 subunit lead to Meier-Gorlin syndrome in humans.
Kanokwan Champasa, Caitlin Blank ... Stephen P Bell
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.
Shalini Gupta, Larry J Friedman ... Stephen P Bell
A single origin–recognition complex (ORC) directs loading of a pair of head-to-head Mcm2-7 replicative DNA helicases by forming a protein tether to the first helicase, releasing from its initial DNA-binding site, and rebinding the origin DNA in the opposite orientation.