ArticleProceedings of the National Academy of Sciences of the United States of America2017
Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers.
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79 citing papers in PubMed.
- Structural insights into Sld3-Sld7-dependent Cdc45 loading during replication initiation.Nature communications · 2026Article
- Mechanisms of MCM2-7 helicase activation and initial DNA melting at near base-pair resolution.Nature communications · 2026Article
- Increased replication-associated single-stranded DNA promotes formaldehyde-induced mutagenesis.bioRxiv : the preprint server for biology · 2026Article
- Assembly of a homohexameric minichromosome maintenance complex is dependent on ATP and DNA.The Journal of biological chemistry · 2026Article
- Archaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation.Nature communications · 2026Article
- An Orc6 tether mediates ORC binding-site switching during replication origin licensing.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Sld3CBD-Cdc45 structural insights into Cdc45 recruitment for CMG complex formation during DNA replication.eLife · 2025Article
- Cell cycle regulation has shaped replication origins in budding yeast.Nature structural & molecular biology · 2025Article
- Compact Origins and Where to Find Them: ORC's Guide to Genome-Wide Licensing.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Mechanisms for licensing origins of DNA replication in eukaryotic cells.Nature structural & molecular biology · 2025Review
- How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?Biochemical Society transactions · 2025Review
- MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.Nature communications · 2025Article
- Sequence specificity of an essential nuclear localization sequence in Mcm3.PLoS genetics · 2025Article
- Structural insights into the mechanism of DNA branch migration during homologous recombination in bacteria.The EMBO journal · 2024Article
- Gene choice in cancer cells is exclusive in ion transport but concurrent in DNA replication.Computational and structural biotechnology journal · 2024Article
- Article
- Open architecture of archaea MCM and dsDNA complexes resolved using monodispersed streptavidin affinity CryoEM.Nature communications · 2024Article
- Sequence specificity of an essential nuclear localization sequence in Mcm3.bioRxiv : the preprint server for biology · 2024Article
- Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex.Nature communications · 2024Article
- MCM2-7 loading-dependent ORC release ensures genome-wide origin licensing.Nature communications · 2024Article
19 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
Abstract
During replication initiation, the core component of the helicase-the Mcm2-7 hexamer-is loaded on origin DNA as a double hexamer (DH). The two ring-shaped hexamers are staggered, leading to a kinked axial channel. How the origin DNA interacts with the axial channel is not understood, but the interaction could provide key insights into Mcm2-7 function and regulation. Here, we report the cryo-EM structure of the Mcm2-7 DH on dsDNA and show that the DNA is zigzagged inside the central channel. Several of the Mcm subunit DNA-binding loops, such as the oligosaccharide-oligonucleotide loops, helix 2 insertion loops, and presensor 1 (PS1) loops, are well defined, and many of them interact extensively with the DNA. The PS1 loops of Mcm 3, 4, 6, and 7, but not 2 and 5, engage the lagging strand with an approximate step size of one base per subunit. Staggered coupling of the two opposing hexamers positions the DNA right in front of the two Mcm2-Mcm5 gates, with each strand being pressed against one gate. The architecture suggests that lagging-strand extrusion initiates in the middle of the DH that is composed of the zinc finger domains of both hexamers. To convert the Mcm2-7 DH structure into the Mcm2-7 hexamer structure found in the active helicase, the N-tier ring of the Mcm2-7 hexamer in the DH-dsDNA needs to tilt and shift laterally. We suggest that these N-tier ring movements cause the DNA strand separation and lagging-strand extrusion.
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