Abstract:
:In eukaryotes, the Cdt1-bound replicative helicase core MCM2-7 is loaded onto DNA by the ORC-Cdc6 ATPase to form a prereplicative complex (pre-RC) with an MCM2-7 double hexamer encircling DNA. Using purified components in the presence of ATP-γS, we have captured in vitro an intermediate in pre-RC assembly that contains a complex between the ORC-Cdc6 and Cdt1-MCM2-7 heteroheptamers called the OCCM. Cryo-EM studies of this 14-subunit complex reveal that the two separate heptameric complexes are engaged extensively, with the ORC-Cdc6 N-terminal AAA+ domains latching onto the C-terminal AAA+ motor domains of the MCM2-7 hexamer. The conformation of ORC-Cdc6 undergoes a concerted change into a right-handed spiral with helical symmetry that is identical to that of the DNA double helix. The resulting ORC-Cdc6 helicase loader shows a notable structural similarity to the replication factor C clamp loader, suggesting a conserved mechanism of action.
journal_name
Nat Struct Mol Bioljournal_title
Nature structural & molecular biologyauthors
Sun J,Evrin C,Samel SA,Fernández-Cid A,Riera A,Kawakami H,Stillman B,Speck C,Li Hdoi
10.1038/nsmb.2629subject
Has Abstractpub_date
2013-08-01 00:00:00pages
944-51issue
8eissn
1545-9993issn
1545-9985pii
nsmb.2629journal_volume
20pub_type
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