ArticleNucleic acids research2014
The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during prereplicative complex formation.
Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 34 citations in OpenAlex.
- H3K4me3 and H3K27ac Promote ccRCC Proliferation Through the CDC6-EXOSC5 Axis.International journal of molecular sciences · 2026Article
- MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis.Nature communications · 2025Article
- Review
- The fungicide pyraclostrobin affects gene expression by altering the DNA methylation pattern inFrontiers in plant science · 2024Article
- The prognostic and immunological role of MCM3 in pan-cancer and validation of prognosis in a clinical lower-grade glioma cohort.Frontiers in pharmacology · 2024Article
- Distinct roles of Arabidopsis ORC1 proteins in DNA replication and heterochromatic H3K27me1 deposition.Nature communications · 2023Article
- The Impact of [C16Pyr][Amp] on the Aggressiveness in Breast and Prostate Cancer Cell Lines.International journal of molecular sciences · 2020Article
- Molecular mechanisms of eukaryotic origin initiation, replication fork progression, and chromatin maintenance.The Biochemical journal · 2020Article
- A novel transcriptional cascade is involved in Fzr-mediated endoreplication.Nucleic acids research · 2020Article
- Norcantharidin inhibits the DDR of bladder cancer stem-like cells through cdc6 degradation.OncoTargets and therapy · 2019Article
- Role of MCM2-7 protein phosphorylation in human cancer cells.Cell & bioscience · 2018Review
- The High-Affinity Interaction between ORC and DNA that Is Required for Replication Licensing Is Inhibited by 2-Arylquinolin-4-Amines.Cell chemical biology · 2017Article
- From structure to mechanism-understanding initiation of DNA replication.Genes & development · 2017Review
- Mechanisms and regulation of DNA replication initiation in eukaryotes.Critical reviews in biochemistry and molecular biology · 2017Review
- Structural basis of Mcm2-7 replicative helicase loading by ORC-Cdc6 and Cdt1.Nature structural & molecular biology · 2017Article
- Cryo-EM of dynamic protein complexes in eukaryotic DNA replication.Protein science : a publication of the Protein Society · 2017Review
- Emerging Roles for Ciz1 in Cell Cycle Regulation and as a Driver of Tumorigenesis.Biomolecules · 2016Review
- Chromosome Duplication in Saccharomyces cerevisiae.Genetics · 2016Review
- Juvenile Hormone Activates the Transcription of Cell-division-cycle 6 (Cdc6) for Polyploidy-dependent Insect Vitellogenesis and Oogenesis.The Journal of biological chemistry · 2016Article
- A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase.Nucleic acids research · 2015Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
The replicative mini-chromosome-maintenance 2-7 (MCM2-7) helicase is loaded in Saccharomyces cerevisiae and other eukaryotes as a head-to-head double-hexamer around origin DNA. At first, ORC/Cdc6 recruits with the help of Cdt1 a single MCM2-7 hexamer to form an 'initial' ORC/Cdc6/Cdt1/MCM2-7 complex. Then, on ATP hydrolysis and Cdt1 release, the 'initial' complex is transformed into an ORC/Cdc6/MCM2-7 (OCM) complex. However, it remains unclear how the OCM is subsequently converted into a MCM2-7 double-hexamer. Through analysis of MCM2-7 hexamer-interface mutants we discovered a complex competent for MCM2-7 dimerization. We demonstrate that these MCM2-7 mutants arrest during prereplicative complex (pre-RC) assembly after OCM formation, but before MCM2-7 double-hexamer assembly. Remarkably, only the OCM complex, but not the 'initial' ORC/Cdc6/Cdt1/MCM2-7 complex, is competent for MCM2-7 dimerization. The MCM2-7 dimer, in contrast to the MCM2-7 double-hexamer, interacts with ORC/Cdc6 and is salt-sensitive, classifying the arrested complex as a helicase-loading intermediate. Accordingly, we found that overexpression of the mutants cause cell-cycle arrest and dominant lethality. Our work identifies the OCM complex as competent for MCM2-7 dimerization, reveals MCM2-7 dimerization as a limiting step during pre-RC formation and defines critical mechanisms that explain how origins are licensed.
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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.