ArticleNature communications2021
The structure of ORC-Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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37 citing papers in PubMed, 67 citations in OpenAlex.
- Porcine Beta Defensin 2 Alleviates Apoptosis and Restores Proliferation in IPEC-J2 Cells Challenged with ETEC K88 by Inhibiting the Akt Signaling Pathway.Probiotics and antimicrobial proteins · 2026Article
- Chromatin architecture sets origin licensing capacity.Research square · 2026Article
- Chromatin architecture sets origin licensing capacity.bioRxiv : the preprint server for biology · 2026Article
- A Meier-Gorlin syndrome mutation impairs the loading of the MCM2-7 complex during DNA replication initiation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- CRISPR spacers reveal diverse and abundant Thermococcales viruses in hydrothermal vents.Research square · 2026Article
- A lethal ORC ATPase mutation is suppressed by alterations in ORC and RNA Pol II transcription components.PloS one · 2026Article
- An inhibitor of UHM splicing factors exerts anti-leukemic activity by altering cell cycle progression and reducing lysosome acidification.Cellular signalling · 2025Article
- CDC6 promotes the development and progression of clear cell renal cell carcinoma via upregulating RRM2.Human cell · 2025Article
- Cell cycle regulation has shaped replication origins in budding yeast.Nature structural & molecular biology · 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
- DNA bending mediated by ORC is essential for replication licensing in budding yeast.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- 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
- 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
- Genome-Wide Mapping of Autonomously Replicating Sequences in the Marine Diatom Phaeodactylum tricornutum.Marine biotechnology (New York, N.Y.) · 2024Article
- The structural landscape of Microprocessor-mediated processing of pri-let-7 miRNAs.Molecular cell · 2024Article
- The Archaeal Cell Cycle.Annual review of cell and developmental biology · 2024Review
- The structural landscape of Microprocessor mediated pri-bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
The Origin Recognition Complex (ORC) binds to sites in chromosomes to specify the location of origins of DNA replication. The S. cerevisiae ORC binds to specific DNA sequences throughout the cell cycle but becomes active only when it binds to the replication initiator Cdc6. It has been unclear at the molecular level how Cdc6 activates ORC, converting it to an active recruiter of the Mcm2-7 hexamer, the core of the replicative helicase. Here we report the cryo-EM structure at 3.3 Å resolution of the yeast ORC-Cdc6 bound to an 85-bp ARS1 origin DNA. The structure reveals that Cdc6 contributes to origin DNA recognition via its winged helix domain (WHD) and its initiator-specific motif. Cdc6 binding rearranges a short α-helix in the Orc1 AAA+ domain and the Orc2 WHD, leading to the activation of the Cdc6 ATPase and the formation of the three sites for the recruitment of Mcm2-7, none of which are present in ORC alone. The results illuminate the molecular mechanism of a critical biochemical step in the licensing of eukaryotic replication origins.
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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.