ArticleMolecular cell2013
An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer assembly.
Article in Molecular cell, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 95 papers.
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Who cites it
95 citing papers in PubMed, 136 citations in OpenAlex.
- H3K4me3 and H3K27ac Promote ccRCC Proliferation Through the CDC6-EXOSC5 Axis.International journal of molecular sciences · 2026Article
- Distinct roles of MCM2-7 subunits in replication licensing in human cells.Nature communications · 2026Article
- Geminin inhibits DNA replication licensing by sterically blocking CDT1-MCM2 interactions.Nature communications · 2025Article
- Regulated TRESLIN-MTBP loading governs initiation zones and replication timing in human DNA replication.Nature communications · 2025Article
- 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
- 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
- BAHCC1 binds H4K20me1 to facilitate the MCM complex loading and DNA replication.Nature communications · 2025Article
- SETD3-mediated histidine methylation of MCM7 regulates DNA replication by facilitating chromatin loading of MCM.Science China. Life sciences · 2025Article
- Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates.Nature communications · 2025Article
- MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.Nature communications · 2025Article
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- Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.Cancer metastasis reviews · 2024Review
- Replication licensing regulated by a short linear motif within an intrinsically disordered region of origin recognition complex.Nature communications · 2024Article
- Multiple pathways for licensing human replication origins.bioRxiv : the preprint server for biology · 2024Article
- Changing protein-DNA interactions promote ORC binding-site exchange during replication origin licensing.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Changing protein-DNA interactions promote ORC binding site exchange during replication origin licensing.bioRxiv : the preprint server for biology · 2023Article
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- An essential Noc3p dimerization cycle mediates ORC double-hexamer formation in replication licensing.Life science alliance · 2023Article
- Review
35 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
In Saccharomyces cerevisiae and higher eukaryotes, the loading of the replicative helicase MCM2-7 onto DNA requires the combined activities of ORC, Cdc6, and Cdt1. These proteins load MCM2-7 in an unknown way into a double hexamer around DNA. Here we show that MCM2-7 recruitment by ORC/Cdc6 is blocked by an autoinhibitory domain in the C terminus of Mcm6. Interestingly, Cdt1 can overcome this inhibitory activity, and consequently the Cdt1-MCM2-7 complex activates ORC/Cdc6 ATP-hydrolysis to promote helicase loading. While Cdc6 ATPase activity is known to facilitate Cdt1 release and MCM2-7 loading, we discovered that Orc1 ATP-hydrolysis is equally important in this process. Moreover, we found that Orc1/Cdc6 ATP-hydrolysis promotes the formation of the ORC/Cdc6/MCM2-7 (OCM) complex, which functions in MCM2-7 double-hexamer assembly. Importantly, CDK-dependent phosphorylation of ORC inhibits OCM establishment to ensure once per cell cycle replication. In summary, this work reveals multiple critical mechanisms that redefine our understanding of DNA licensing.
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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.