ArticleNature communications2024
Structures of the human leading strand Polε-PCNA holoenzyme.
Article in Nature communications, 2024. 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 12 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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
12 citing papers in PubMed.
- Interpreting the effects of DNA polymerase variants at the structural level.Molecular oncology · 2026Article
- The RecBCD complex interacts directly with the DNA sliding clamp in Escherichia coli.Nucleic acids research · 2026Article
- USP1 inhibition promotes RAD18-dependent PCNA degradation and BRCA1 synthetic lethality.bioRxiv : the preprint server for biology · 2026Article
- A thumb-domain insertion balances processivity and fidelity in DNA polymerase ε.Nucleic acids research · 2026Article
- Article
- The genetic and biochemical basis of human leading strand synthesis.Nature communications · 2025Article
- Evidence for a functional interaction between yeast Pol ε and PCNA in vivo.Nucleic acids research · 2025Article
- Targeting RAD52 overcomes PARP inhibitor resistance in preclinicalbioRxiv : the preprint server for biology · 2025Article
- The proofreading mechanism of the human leading-strand DNA polymerase ε holoenzyme.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Functional asymmetry in processivity clamp proteins.Biophysical journal · 2025Review
- A conserved thumb domain insertion in DNA polymerase epsilon supports processive DNA synthesis.Nucleic acids research · 2025Article
- Clamping Pol ε to the leading strand.Nature structural & molecular biology · 2024Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors.
Funding
Abstract
In eukaryotes, the leading strand DNA is synthesized by Polε and the lagging strand by Polδ. These replicative polymerases have higher processivity when paired with the DNA clamp PCNA. While the structure of the yeast Polε catalytic domain has been determined, how Polε interacts with PCNA is unknown in any eukaryote, human or yeast. Here we report two cryo-EM structures of human Polε-PCNA-DNA complex, one in an incoming nucleotide bound state and the other in a nucleotide exchange state. The structures reveal an unexpected three-point interface between the Polε catalytic domain and PCNA, with the conserved PIP (PCNA interacting peptide)-motif, the unique P-domain, and the thumb domain each interacting with a different protomer of the PCNA trimer. We propose that the multi-point interface prevents other PIP-containing factors from recruiting to PCNA while PCNA functions with Polε. Comparison of the two states reveals that the finger domain pivots around the [4Fe-4S] cluster-containing tip of the P-domain to regulate nucleotide exchange and incoming nucleotide binding.
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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.