Multiple Functions for Mcm2–7 ATPase Motifs during Replication Initiation
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Bell_Multiple functions.pdf
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Checksum (MD5)
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Author(s)
Kang, Sukhyun
Warner, Megan Dobbins
Bell, Stephen P
Date Issued
July 2014
Journal
Molecular Cell
Publisher
Elsevier
Citation
Kang, Sukhyun; Warner, Megan D. and Bell, Stephen P. “Multiple Functions for Mcm2–7 ATPase Motifs During Replication Initiation.” Molecular Cell 55, no. 5 (September 2014): 655–665 © 2014 Elsevier Inc
Version
Author's final manuscript
Abstract
The Mcm2–7 replicative helicase is central to all steps of eukaryotic DNA replication. The hexameric ring of Mcm subunits forms six essential ATPases whose contributions to replication initiation remain unclear. Mcm2–7 complexes containing ATPase-motif mutations showed Mcm2–7 ATP binding and hydrolysis are required for helicase loading. Loading-defective Mcm2–7 mutant complexes were defective in initial Mcm2–7 recruitment or Cdt1 release. Comparison with Cdc6 ATPase mutants showed that Cdc6 ATP hydrolysis is not required for helicase loading but instead drives removal of Mcm2–7 complexes that cannot complete loading. A subset of Mcm2–7 ATPase-site mutants completed helicase loading but could not initiate replication. Individual mutants were defective in distinct events during helicase activation, including maintenance of DNA association, recruitment of the GINS helicase activator, and DNA unwinding. Consistent with its heterohexameric structure, our findings show that the six Mcm2–7 ATPase active sites are specialized for different functions during helicase loading and activation.
MIT Department
Massachusetts Institute of Technology. Department of Biology
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/j.molcel.2014.06.033
