ArticleProceedings of the National Academy of Sciences of the United States of America2015
Cdc45 (cell division cycle protein 45) guards the gate of the Eukaryote Replisome helicase stabilizing leading strand engagement.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed.
- Archaeal and eukaryotic MCM rings sequentially melt DNA for replication initiation.Nature communications · 2026Article
- DNA translocation by the CMG helicase: the helical inchworm model.Biochemical Society transactions · 2026Review
- Identification of a novel and a recurrentFrontiers in genetics · 2026Article
- Analyzing DNA Replication Fork Stability and Collapse Using Chromatin Fiber Analysis and the R-ODD-BLOBS Program.Computational and structural biotechnology journal · 2026Article
- Modelling DNA replication fork stability and collapse using chromatin fiber analysis and the R-ODD-BLOBS program.bioRxiv : the preprint server for biology · 2025Article
- HSF2 drives breast cancer progression by acting as a stage-specific switch between proliferation and invasion.Science advances · 2025Article
- Identification of key biomarker genes in liver hepatocellular carcinoma and kidney renal clear cell carcinoma progression: A shared high-throughput screening and molecular docking method with potentials for targeted therapeutic interventions.Journal, genetic engineering & biotechnology · 2025Article
- Unidirectional MCM translocation away from ORC drives origin licensing.Nature communications · 2025Article
- p65 signaling dynamics drive the developmental progression of hematopoietic stem and progenitor cells through cell cycle regulation.Nature communications · 2024Article
- Unwinding Helicase MCM Functionality for Diagnosis and Therapeutics of Replication Abnormalities Associated with Cancer: A Review.Molecular diagnosis & therapy · 2024Review
- Visfatin Affects the Transcriptome of Porcine Luteal Cells during Early Pregnancy.International journal of molecular sciences · 2024Article
- Embracing Heterogeneity: Challenging the Paradigm of Replisomes as Deterministic Machines.Chemical reviews · 2023Review
- Episomal and chromosomal DNA replication and recombination inFrontiers in molecular biosciences · 2023Review
- CMG helicase can use ATPγS to unwind DNA: Implications for the rate-limiting step in the reaction mechanism.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- CMG helicase activity on G4-containing DNA templates.Methods in enzymology · 2022Article
- Synergistic effects of methyl 2-cyano-3,11-dioxo-18beta-olean-1,-12-dien-30-oate and erlotinib on erlotinib-resistant non-small cell lung cancer cells.Journal of pharmaceutical analysis · 2021Article
- Mechanisms of hexameric helicases.Critical reviews in biochemistry and molecular biology · 2021Review
- Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms.International journal of molecular sciences · 2021Review
- Single-Molecule Insights Into the Dynamics of Replicative Helicases.Frontiers in molecular biosciences · 2021Review
- The plasticity of DNA replication forks in response to clinically relevant genotoxic stress.Nature reviews. Molecular cell biology · 2020Review
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Authors and funding
7 authors.
Funding
Abstract
DNA replication licensing is now understood to be the pathway that leads to the assembly of double hexamers of minichromosome maintenance (Mcm2-7) at origin sites. Cell division control protein 45 (Cdc45) and GINS proteins activate the latent Mcm2-7 helicase by inducing allosteric changes through binding, forming a Cdc45/Mcm2-7/GINS (CMG) complex that is competent to unwind duplex DNA. The CMG has an active gate between subunits Mcm2 and Mcm5 that opens and closes in response to nucleotide binding. The consequences of inappropriate Mcm2/5 gate actuation and the role of a side channel formed between GINS/Cdc45 and the outer edge of the Mcm2-7 ring for unwinding have remained unexplored. Here we uncover a novel function for Cdc45. Cross-linking studies trace the path of the DNA with the CMG complex at a fork junction between duplex and single strands with the bound CMG in an open or closed gate conformation. In the closed state, the lagging strand does not pass through the side channel, but in the open state, the leading strand surprisingly interacts with Cdc45. Mutations in the recombination protein J fold of Cdc45 that ablate this interaction diminish helicase activity. These data indicate that Cdc45 serves as a shield to guard against occasional slippage of the leading strand from the core channel.
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