Evidence map›Paper›PMID 35829698›Full record

ArticleeLife2022

Cryo-EM structures reveal that RFC recognizes both the 3'- and 5'-DNA ends to load PCNA onto gaps for DNA repair.

Fengwei Zheng, Roxana Georgescu, Nina Y Yao, Huilin Li, Michael E O'Donnell

Open access · goldAbstract read
In one paragraph

Article in eLife, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed, 35 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Mechanistic diversity of clamp loading at small DNA gaps.The Journal of biological chemistry · 2026
    Review
  5. Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. ThebioRxiv : the preprint server for biology · 2026
    Article
  13. Article
  14. Article
  15. PCNA is a nucleotide exchange factor for the clamp loader ATPase complex.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  16. DNA polymerase α-primase can function as a translesion DNA polymerase.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  17. Article
  18. PCNA is a Nucleotide Exchange Factor for the Clamp Loader ATPase Complex.bioRxiv : the preprint server for biology · 2025
    Article
  19. 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 · 2025
    Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 1 country.

Fengwei ZhengDepartment of Structural Biology, Van Andel Institute, Grand Rapids, United States.ORCID 0000-0002-7139-4831
Roxana GeorgescuDNA Replication Laboratory, The Rockefeller University, New York, United States.ORCID 0000-0002-1882-2358
Nina Y YaoDNA Replication Laboratory, The Rockefeller University, New York, United States.
Huilin LiDepartment of Structural Biology, Van Andel Institute, Grand Rapids, United States.ORCID 0000-0001-8085-8928
Michael E O'DonnellDNA Replication Laboratory, The Rockefeller University, New York, United States.ORCID 0000-0001-9002-4214
Rockefeller University · USVan Andel Institute · USHoward Hughes Medical Institute · US

Funding

Structural mechanism of DNA replicationR35GM131754 · NIGMS · VAN ANDEL RESEARCH INSTITUTE · PI Huilin Li · 2019 to 2026
$6.0M
Biochemical Mechanism and Structure of the Eukaryotic Replication ForkR01GM115809 · NIGMS · ROCKEFELLER UNIVERSITY · PI O'DONNELL, MICHAEL E · 2015 to 2022
$2.6M
NIGMS NIH HHS R01 GM115809NIGMS NIH HHS R35 GM131754
6 · The paper itself

Abstract

RFC uses ATP to assemble PCNA onto primed sites for replicative DNA polymerases δ and ε. The RFC pentamer forms a central chamber that binds 3' ss/ds DNA junctions to load PCNA onto DNA during replication. We show here five structures that identify a second DNA binding site in RFC that binds a 5' duplex. This 5' DNA site is located between the N-terminal BRCT domain and AAA+ module of the large Rfc1 subunit. Our structures reveal ideal binding to a 7-nt gap, which includes 2 bp unwound by the clamp loader. Biochemical studies show enhanced binding to 5 and 10 nt gaps, consistent with the structural results. Because both 3' and 5' ends are present at a ssDNA gap, we propose that the 5' site facilitates RFC's PCNA loading activity at a DNA damage-induced gap to recruit gap-filling polymerases. These findings are consistent with genetic studies showing that base excision repair of gaps greater than 1 base requires PCNA and involves the 5' DNA binding domain of Rfc1. We further observe that a 5' end facilitates PCNA loading at an RPA coated 30-nt gap, suggesting a potential role of the RFC 5'-DNA site in lagging strand DNA synthesis.

Indexed as

DNASaccharomyces cerevisiae ProteinsCryoelectron MicroscopyDNA RepairDNA ReplicationProliferating Cell Nuclear AntigenProtein BindingReplication Protein CDNAProliferating Cell Nuclear AntigenReplication Protein CSaccharomyces cerevisiae Proteinsbiochemistrychemical biologyDNA damageDNA repairDNA replicationPCNARFCS. cerevisiaesliding clamp

Identifiers

PMID35829698
PMCPMC9293004
OpenAlexW4285392258

What OpenQuestion holds

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LicenceCC BY
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Registered trials

None linked

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.