ArticleeLife2019
A conserved Mcm4 motif is required for Mcm2-7 double-hexamer formation and origin DNA unwinding.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Archaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation.Nature communications · 2026Article
- Minichromosome maintenance 4 plays a key role in protecting against acute kidney injury by regulating tubular epithelial cells survival and regeneration.Journal of advanced research · 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
- Transcription factor E2F1 promotes non-small cell lung cancer progression by activating the PI3K/AKT pathway through MCM4.Journal of cardiothoracic surgery · 2025Article
- The Slx4-Rad1-Rad10 nuclease differentially regulates deletions and duplications induced by a replication fork barrier.PLoS genetics · 2025Article
- Article
- Essential and multifunctional mpox virus E5 helicase-primase in double and single hexamer.Science advances · 2024Article
- Unwinding of a eukaryotic origin of replication visualized by cryo-EM.Nature structural & molecular biology · 2024Article
- Alkynyl nicotinamides show antileukemic activity in drug-resistant acute myeloid leukemia.The Journal of clinical investigation · 2024Article
- Multiple pathways for licensing human replication origins.bioRxiv : the preprint server for biology · 2024Article
- Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines.Chemical reviews · 2023Review
- Identifying the personalized driver gene sets maximally contributing to abnormality of transcriptome phenotype in glioblastoma multiforme individuals.Molecular oncology · 2023Article
- 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
- Nucleotide binding halts diffusion of the eukaryotic replicative helicase during activation.Nature communications · 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
- In silico reconstitution of DNA replication. Lessons from single-molecule imaging and cryo-tomography applied to single-particle cryo-EM.Current opinion in structural biology · 2022Review
- MCM4 is a novel prognostic biomarker and promotes cancer cell growth in glioma.Frontiers in oncology · 2022Article
- Comprehensive Analysis of the Expression and Prognosis for MCM4 in Uterine Corpus Endometrial Carcinoma.Frontiers in genetics · 2022Article
- Structural mechanism for the selective phosphorylation of DNA-loaded MCM double hexamers by the Dbf4-dependent kinase.Nature structural & molecular biology · 2022Article
- Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Licensing of eukaryotic origins of replication requires DNA loading of two copies of the Mcm2-7 replicative helicase to form a head-to-head double-hexamer, ensuring activated helicases depart the origin bidirectionally. To understand the formation and importance of this double-hexamer, we identified mutations in a conserved and essential Mcm4 motif that permit loading of two Mcm2-7 complexes but are defective for double-hexamer formation. Single-molecule studies show mutant Mcm2-7 forms initial hexamer-hexamer interactions; however, the resulting complex is unstable. Kinetic analyses of wild-type and mutant Mcm2-7 reveal a limited time window for double-hexamer formation following second Mcm2-7 association, suggesting that this process is facilitated. Double-hexamer formation is required for extensive origin DNA unwinding but not initial DNA melting or recruitment of helicase-activation proteins (Cdc45, GINS, Mcm10). Our findings elucidate dynamic mechanisms of origin licensing, and identify the transition between initial DNA melting and extensive unwinding as the first initiation event requiring double-hexamer formation.
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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.