Mcm10 regulates DNA replication elongation by stimulating the CMG replicative helicase
Name
Looke-Mcm10 regulates DNA replication elo.pdf
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1.66 MB
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Adobe PDF
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Author(s)
Looke, Marko
Maloney, Michael Finnan
Bell, Stephen P
Date Issued
February 2017
Journal
Genes & Development
Publisher
Cold Spring Harbor Laboratory Press
Citation
Lõoke, Marko, et al. “Mcm10 Regulates DNA Replication Elongation by Stimulating the CMG Replicative Helicase.” Genes & Development 31, 3 (February 2017): 291–305 © 2017 Lõoke et al
Version
Final published version
Abstract
Activation of the Mcm2–7 replicative DNA helicase is the committed step in eukaryotic DNA replication initiation. Although Mcm2–7 activation requires binding of the helicase-activating proteins Cdc45 and GINS (forming the CMG complex), an additional protein, Mcm10, drives initial origin DNA unwinding by an unknown mechanism. We show that Mcm10 binds a conserved motif located between the oligonucleotide/oligosaccharide fold (OB-fold) and A subdomain of Mcm2. Although buried in the interface between these domains in Mcm2–7 structures, mutations predicted to separate the domains and expose this motif restore growth to conditional-lethal MCM10 mutant cells. We found that, in addition to stimulating initial DNA unwinding, Mcm10 stabilizes Cdc45 and GINS association with Mcm2–7 and stimulates replication elongation in vivo and in vitro. Furthermore, we identified a lethal allele of MCM10 that stimulates initial DNA unwinding but is defective in replication elongation and CMG binding. Our findings expand the roles of Mcm10 during DNA replication and suggest a new model for Mcm10 function as an activator of the CMG complex throughout DNA replication.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution-NonCommercial 4.0 International
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DOI of Published Version
https://doi.org/10.1101/gad.291336.116
