ArticleNature2014
A Ctf4 trimer couples the CMG helicase to DNA polymerase α in the eukaryotic replisome.
Article in Nature, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 148 papers.
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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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Who cites it
148 citing papers in PubMed, 213 citations in OpenAlex.
- An updated view on lagging strand DNA replication: implications for the replication stress response.Cell cycle (Georgetown, Tex.) · 2026Article
- Switch from canonical to recombination-dependent DNA synthesis by M-CDK phosphorylation of DNA Polα.The EMBO journal · 2026Article
- FACT-(H3-H4) complex stimulates Pol α activity to coordinate DNA synthesis with nucleosome assembly.Science advances · 2026Article
- Inhibition of lagging strand replication by G-rich telomeric DNA and the shelterin subunit POT1.The EMBO journal · 2026Article
- DNA Polymerase α has pyrimidine dimer translesion activity that is suppressed during normal replication.bioRxiv : the preprint server for biology · 2026Article
- Proximal proteomics analysis reveals DNA polymerase δ subunit 3 is a new MCM2 binding partner and promotes parental histones inheritance in mammalian cells.Cell death and differentiation · 2026Article
- DNA translocation by the CMG helicase: the helical inchworm model.Biochemical Society transactions · 2026Review
- Fork Reversal Safeguards Epigenetic Inheritance During Replication Stress.Research square · 2026Article
- Replisome passage through the cohesin ring.Cell · 2025Article
- AND-1 is a critical regulator of R-loop dynamics and a target to overcome endocrine resistance.Science advances · 2025Article
- Aere perennius: how chromatin fidelity is maintained and lost in disease.NAR molecular medicine · 2025Review
- DNA polymerase α/primase extraction from chromatin by VCP/p97 restricts ATR activation during unperturbed DNA replication.Nature communications · 2025Article
- Nucleosomes represent a crucial target for the intra-S phase checkpoint in response to replication stress.Science advances · 2025Article
- A Rfa1-MN-based system reveals new factors involved in the rescue of broken replication forks.PLoS genetics · 2025Article
- Control of Replication Stress Response by Cytosolic Fe-S Cluster Assembly (CIA) Machinery.Cells · 2025Review
- A tale of two strands: Decoding chromatin replication through strand-specific sequencing.Molecular cell · 2025Review
- Stabilization of expandable DNA repeats by the replication factor Mcm10 promotes cell viability.Nature communications · 2024Article
- Multifaceted role of the DNA replication protein MCM10 in maintaining genome stability and its implication in human diseases.Cancer metastasis reviews · 2024Review
- Four decades of Eukaryotic DNA replication: From yeast genetics to high-resolution cryo-EM structures of the replisome.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The multifaceted roles of the Ctf4 replisome hub in the maintenance of genome integrity.DNA repair · 2024Review
88 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 1 country.
Funding
Abstract
Efficient duplication of the genome requires the concerted action of helicase and DNA polymerases at replication forks to avoid stalling of the replication machinery and consequent genomic instability. In eukaryotes, the physical coupling between helicase and DNA polymerases remains poorly understood. Here we define the molecular mechanism by which the yeast Ctf4 protein links the Cdc45-MCM-GINS (CMG) DNA helicase to DNA polymerase α (Pol α) within the replisome. We use X-ray crystallography and electron microscopy to show that Ctf4 self-associates in a constitutive disk-shaped trimer. Trimerization depends on a β-propeller domain in the carboxy-terminal half of the protein, which is fused to a helical extension that protrudes from one face of the trimeric disk. Critically, Pol α and the CMG helicase share a common mechanism of interaction with Ctf4. We show that the amino-terminal tails of the catalytic subunit of Pol α and the Sld5 subunit of GINS contain a conserved Ctf4-binding motif that docks onto the exposed helical extension of a Ctf4 protomer within the trimer. Accordingly, we demonstrate that one Ctf4 trimer can support binding of up to three partner proteins, including the simultaneous association with both Pol α and GINS. Our findings indicate that Ctf4 can couple two molecules of Pol α to one CMG helicase within the replisome, providing a new model for lagging-strand synthesis in eukaryotes that resembles the emerging model for the simpler replisome of Escherichia coli. The ability of Ctf4 to act as a platform for multivalent interactions illustrates a mechanism for the concurrent recruitment of factors that act together at the fork.
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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.