Loading mechanisms of ring helicases at replication origins.
Bottom Line: Bidirectional loading of two ring helicases at a replication origin is achieved by strictly regulated and intricately choreographed mechanisms, often through the action of replication initiation and helicase-loader proteins.Current structural and biochemical data reveal a wide range of different helicase-loading mechanisms.Here we review advances in this area and discuss their implications.
Affiliation: School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK. firstname.lastname@example.orgShow MeSH
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Mentions: In A. aeolicus, the DnaC helicase loader cooperates with the replication initiator DnaA to load two ring helicases at the replication origin. The DnaA and DnaC nucleoprotein filaments described above are directional. One end of the filament terminates with a protein molecule (DnaA or DnaC) presenting an ATP-bound active site in the open state, defined as the ATP-end, and the opposite end of the filament terminates with a protein molecule presenting the arginine finger of Box VII, defined as the R-end (Fig. 1B and Mott et al., 2008). Initial binding of DnaA molecules to DnaA boxes, via the C-terminal domain IV, at the oriC forms a directional right-handed helical filament with the DNA double helix wrapped around the outside of the filament and the ATP-end directed towards the DUE. The constrained positive supercoiling induces compensatory negative supercoiling and weakening of the double helix within the DUE. Partial melting of the DUE at the ATP-end of the filament exposes the two DNA strands and the DnaA filament invades one of the strands forming an extended filament, with the single-stranded DNA bound along the contiguous network of the α3/α4 and α5/α6 helices inside the DnaA filament (Fig. 2A and Duderstadt et al., 2011). Therefore, the role of DnaA is initially to destabilize and actively melt the DUE at the replication origin.
Affiliation: School of Chemistry, Centre for Biomolecular Sciences, University of Nottingham, University Park, Nottingham NG7 2RD, UK. email@example.com