ArticleeLife2021
A helicase-tethered ORC flip enables bidirectional helicase loading.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
What it found
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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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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 40 citations in OpenAlex.
- Chromatin architecture sets origin licensing capacity.Research square · 2026Article
- Chromatin architecture sets origin licensing capacity.bioRxiv : the preprint server for biology · 2026Article
- Distinct roles of MCM2-7 subunits in replication licensing in human cells.Nature communications · 2026Article
- Dynamic DnaA-DnaB interactions at oriC coordinate the loading and coupled translocation of two DnaB helicases for bidirectional replication.Nucleic acids research · 2026Article
- A lethal ORC ATPase mutation is suppressed by alterations in ORC and RNA Pol II transcription components.PloS one · 2026Article
- Correlating membrane-protein dynamics with function: Integrating bioinformatics, molecular dynamics, and single-molecule FRET.Protein science : a publication of the Protein Society · 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
- 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
- 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
- Article
- 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
- Multiple pathways for licensing human replication origins.bioRxiv : the preprint server for biology · 2024Article
- Identification of 1600 replication origins ineLife · 2024Article
- The Origin Recognition Complex: From Origin Selection to Replication Licensing in Yeast and Humans.Biology · 2023Review
- Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines.Chemical reviews · 2023Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Replication origins are licensed by loading two Mcm2-7 helicases around DNA in a head-to-head conformation poised to initiate bidirectional replication. This process requires origin-recognition complex (ORC), Cdc6, and Cdt1. Although different Cdc6 and Cdt1 molecules load each helicase, whether two ORC proteins are required is unclear. Using colocalization single-molecule spectroscopy combined with single-molecule Förster resonance energy transfer (FRET), we investigated interactions between ORC and Mcm2-7 during helicase loading. In the large majority of events, we observed a single ORC molecule recruiting both Mcm2-7/Cdt1 complexes via similar interactions that end upon Cdt1 release. Between first- and second-helicase recruitment, a rapid change in interactions between ORC and the first Mcm2-7 occurs. Within seconds, ORC breaks the interactions mediating first Mcm2-7 recruitment, releases from its initial DNA-binding site, and forms a new interaction with the opposite face of the first Mcm2-7. This rearrangement requires release of the first Cdt1 and tethers ORC as it flips over the first Mcm2-7 to form an inverted Mcm2-7-ORC-DNA complex required for second-helicase recruitment. To ensure correct licensing, this complex is maintained until head-to-head interactions between the two helicases are formed. Our findings reconcile previous observations and reveal a highly coordinated series of events through which a single ORC molecule can load two oppositely oriented helicases.
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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.