FIG. 6.

Replication initiation sites are coincident with MCM but not ORC. ORC (white) binding to DNA is promiscuous, and a mechanism for selective binding of ORC to DNA relies on differences in chromatin structure (e.g., methylation) that exclude ORC from chromatin (black plasmid DNA). Once ORC binds to accessible chromatin (white insert DNA), multiple MCMs (gray) are loaded in a cdc6 (black)- and cdt1 (not shown)-dependent manner and occupy DNA sites at least 1 kb distal to ORC. Sites of replication initiation are detectable in a broad region and, like MCM binding, are detectable at distant regions of DNA that are negative for ORC binding.