Mechanism and timing of Mcm2–7 ring closure during DNA replication origin licensing
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Author(s)
Ticau, Simina
Friedman, Larry J
Champasa, Kanokwan
Corrêa, Ivan R
Gelles, Jeff
Bell, Stephen P
Date Issued
March 2017
Journal
Nature Structural & Molecular Biology
Publisher
Springer Nature
Citation
Ticau, Simina, et al. “Mechanism and Timing of Mcm2–7 Ring Closure during DNA Replication Origin Licensing.” Nature Structural & Molecular Biology, vol. 24, no. 3, Mar. 2017, pp. 309–15.
Version
Author's final manuscript
Abstract
The opening and closing of two ring-shaped Mcm2-7 DNA helicases is necessary to license eukaryotic origins of replication, although the mechanisms controlling these events are unclear. The origin-recognition complex (ORC), Cdc6 and Cdt1 facilitate this process by establishing a topological link between each Mcm2-7 hexamer and origin DNA. Using colocalization single-molecule spectroscopy and single-molecule Förster resonance energy transfer (FRET), we monitored ring opening and closing of Saccharomyces cerevisiae Mcm2-7 during origin licensing. The two Mcm2-7 rings were open during initial DNA association and closed sequentially, concomitant with the release of their associated Cdt1. We observed that ATP hydrolysis by Mcm2-7 was coupled to ring closure and Cdt1 release, and failure to load the first Mcm2-7 prevented recruitment of the second Mcm2-7. Our findings identify key mechanisms controlling the Mcm2-7 DNA-entry gate during origin licensing, and reveal that the two Mcm2-7 complexes are loaded via a coordinated series of events with implications for bidirectional replication initiation and quality control.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1038/NSMB.3375
