MCM Loading—An Open-and-Shut Case? Rachel Y. Samson, Stephen D. Bell  Molecular Cell  Volume 50, Issue 4, Pages 457-458 (May 2013) DOI: 10.1016/j.molcel.2013.05.008 Copyright © 2013 Elsevier Inc. Terms and Conditions

Figure 1 Model for Prereplicative Complex Formation (A) MCM(2-7) is recruited to DNA-bound ORC•Cdc6 via the C terminus of Mcm3. Without Cdt1, MCM(2, 4, 6) in the recruited complex is greatly destabilized. (B) [1] Cdt1 binds to and inactivates an autoinhibitory C-terminal tail of Mcm6. [2] In the presence of Cdt1, recruitment of all six MCM subunits to ORC•Cdc6 is mediated by at least two interactions, one with Mcm3 and another via Cdt1. [3] When all components of the prereplicative complex are successfully recruited, ATP hydrolysis by both Orc1 and Cdc6 leads to the release of Cdt1 and formation of the OCM complex (Fernández-Cid et al., 2013). We speculate that as Cdt1 is lost from this complex, MCM(2, 4, 6) may reorganize into an open-book configuration based on a head-to-head interaction with the N-terminal domains of MCM(3, 5, 7). [4] A second MCM(2-7)•Cdt1 complex is then recruited to ORC•Cdc6 utilizing the same interaction interfaces as the first hexamer (Frigola et al., 2013; Fernández-Cid et al., 2013). We speculate further that this displaces the original MCM(3, 5, 7) assembly from ORC•Cdc6, allowing it to reorganize into an intact MCM(2-7) hexamer with MCM(2, 4, 6) that is stabilized by head-to-head interactions with the newly recruited hexamer. [5] Following ATP hydrolysis, Cdt1 and Cdc6 are released from the complex. Molecular Cell 2013 50, 457-458DOI: (10.1016/j.molcel.2013.05.008) Copyright © 2013 Elsevier Inc. Terms and Conditions