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.

The initiation of human genome replication requires the six-subunit origin recognition complex (ORC) and CDC6, with ORC playing additional roles during mitosis and in organization of the cell nucleus.

The human Origin Replication Complex is shaped as a shallow corkscrew in a classic AAA+ organization reminiscent of clamp loader complexes with highly controlled ATPase activity as exemplified by Meier-Gorlin syndrome mutations.

The origin recognition complex is a dynamic complex that assumes various conformational states that likely correspond to different steps in replication initiation.

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.

Human cell lines replicate and proliferate without ORC1 or ORC2, two subunits of the replication initiator protein complex ORC, which has till now been considered essential for DNA replication.

Human cells that lack a subunit in their origin recognition complex are viable, which suggests the existence of alternative mechanisms to initiate DNA replication.

As a cell prepares to divide, a molecular actor known as the Origin Recognition Complex makes intricate ATP-driven movements to recruit proteins required to duplicate DNA.

Origin recognition complex-associated (ORCA) is crucial for the stability of the Histone H3 lysine 9 methyltransferase megacomplex, which is essential for heterochromatin organization.

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.