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.
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.
Structure-guided biochemistry defines how the coupling between nucleic acid substrate binding and ATPase activity is used by a molecular switch to load ring-shaped motor proteins onto single-stranded DNA.
Nucleosomal DNAs assembled or modified by different chromatin remodeling enzymes differentially impact the origin licensing and helicase activation steps of replication initiation.
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.
The origin recognition complex is a dynamic complex that assumes various conformational states that likely correspond to different steps in replication initiation.
Erin A Bassett, Nicholas Tokarew ... Valerie A Wallace
The earliest steps of tumor initiation in the cerebellum are regulated by critical interactions between pre-tumor cells and stromal cells, which can be manipulated by targeting the Norrin/Frizzled4 signaling axis.
Hsiang-Chen Chou, Kuhulika Bhalla ... Bruce Stillman
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.
Two related DNA replication initiation proteins contribute to the decision of whether to enter a new round of the cell division cycle or enter into a period of proliferative quiescence.