ArticleGenes & development2014
A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2-7 onto DNA.
Article in Genes & development, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
82 citing papers in PubMed, 133 citations in OpenAlex.
- Mechanisms of MCM2-7 helicase activation and initial DNA melting at near base-pair resolution.Nature communications · 2026Article
- Distinct roles of MCM2-7 subunits in replication licensing in human cells.Nature communications · 2026Article
- Co-Treatment With rhBMP-2 and Rapamycin Modulates Osteogenesis-Adipogenesis Balance to Enhance Aged Bone Regeneration.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- DNA translocation by the CMG helicase: the helical inchworm model.Biochemical Society transactions · 2026Review
- Sld3CBD-Cdc45 structural insights into Cdc45 recruitment for CMG complex formation during DNA replication.eLife · 2025Article
- Mechanisms for licensing origins of DNA replication in eukaryotic cells.Nature structural & molecular biology · 2025Review
- 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
- How similar are the molecular mechanisms of yeast and metazoan genome replication initiation?Biochemical Society transactions · 2025Review
- Unidirectional MCM translocation away from ORC drives origin licensing.Nature communications · 2025Article
- Article
- Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Multiple pathways for licensing human replication origins.bioRxiv : the preprint server for biology · 2024Article
- Review
- Article
- Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2-7 ring closing.bioRxiv : the preprint server for biology · 2023Article
- Cryo-EM structure of human hexameric MCM2-7 complex.iScience · 2022Article
- Creation and resolution of non-B-DNA structural impediments during replication.Critical reviews in biochemistry and molecular biology · 2022Article
- The Role of MTBP as a Replication Origin Firing Factor.Biology · 2022Review
- A mechanism of origin licensing control through autoinhibition of S. cerevisiae ORC·DNA·Cdc6.Nature communications · 2022Article
22 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
The regulated loading of the replicative helicase minichromosome maintenance proteins 2-7 (MCM2-7) onto replication origins is a prerequisite for replication fork establishment and genomic stability. Origin recognition complex (ORC), Cdc6, and Cdt1 assemble two MCM2-7 hexamers into one double hexamer around dsDNA. Although the MCM2-7 hexamer can adopt a ring shape with a gap between Mcm2 and Mcm5, it is unknown which Mcm interface functions as the DNA entry gate during regulated helicase loading. Here, we establish that the Saccharomyces cerevisiae MCM2-7 hexamer assumes a closed ring structure, suggesting that helicase loading requires active ring opening. Using a chemical biology approach, we show that ORC-Cdc6-Cdt1-dependent helicase loading occurs through a unique DNA entry gate comprised of the Mcm2 and Mcm5 subunits. Controlled inhibition of DNA insertion triggers ATPase-driven complex disassembly in vitro, while in vivo analysis establishes that Mcm2/Mcm5 gate opening is essential for both helicase loading onto chromatin and cell cycle progression. Importantly, we demonstrate that the MCM2-7 helicase becomes loaded onto DNA as a single hexamer during ORC/Cdc6/Cdt1/MCM2-7 complex formation prior to MCM2-7 double hexamer formation. Our study establishes the existence of a unique DNA entry gate for regulated helicase loading, revealing key mechanisms in helicase loading, which has important implications for helicase activation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.