Evidence map›Paper›PMID 35314830›Full record

ArticleNature structural & molecular biology2022

DNA is loaded through the 9-1-1 DNA checkpoint clamp in the opposite direction of the PCNA clamp.

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

Open access · hybridAbstract read
In one paragraph

Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
2.7field-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

26 citing papers in PubMed, 33 citations in OpenAlex.

  1. Mechanistic diversity of clamp loading at small DNA gaps.The Journal of biological chemistry · 2026
    Review
  2. Article
  3. Article
  4. Article
  5. ThebioRxiv : the preprint server for biology · 2026
    Article
  6. Article
  7. 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
  8. Review
  9. The 9-1-1 complex protects ssDNA gaps in BRCA2-deficient cancer.bioRxiv : the preprint server for biology · 2025
    Article
  10. PCNA is a Nucleotide Exchange Factor for the Clamp Loader ATPase Complex.bioRxiv : the preprint server for biology · 2025
    Article
  11. DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025
    Review
  12. Article
  13. Article
  14. Cryo-EM reveals a nearly complete PCNA loading process and unique features of the human alternative clamp loader CTF18-RFC.Proceedings of the National Academy of Sciences of the United States of America · 2024
    Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Differences in clamp loader mechanism between bacteria and eukaryotes.bioRxiv : the preprint server for biology · 2023
    Article
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, MI, USA.ORCID http://orcid.org/0000-0002-7139-4831
Roxana E GeorgescuDNA Replication Laboratory, The Rockefeller University, New York, NY, USA.
Nina Y YaoDNA Replication Laboratory, The Rockefeller University, New York, NY, USA.
Michael E O'DonnellDNA Replication Laboratory, The Rockefeller University, New York, NY, USA. odonnel@rockefeller.edu.ORCID http://orcid.org/0000-0001-9002-4214
Huilin LiDepartment of Structural Biology, Van Andel Institute, Grand Rapids, MI, USA. huilin.li@vai.org.ORCID http://orcid.org/0000-0001-8085-8928
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
The structure and function of eukaryotic protein glycosylation enzymesR01CA231466 · NCI · VAN ANDEL RESEARCH INSTITUTE · PI Huilin Li · 2018 to 2026
$4.0M
Biochemical Mechanism and Structure of the Eukaryotic Replication ForkR01GM115809 · NIGMS · ROCKEFELLER UNIVERSITY · PI O'DONNELL, MICHAEL E · 2015 to 2022
$2.6M
Howard Hughes Medical InstituteNIGMS NIH HHS R01 GM115809NIGMS NIH HHS R35 GM131754
6 · The paper itself

Abstract

The 9-1-1 DNA checkpoint clamp is loaded onto 5'-recessed DNA to activate the DNA damage checkpoint that arrests the cell cycle. The 9-1-1 clamp is a heterotrimeric ring that is loaded in Saccharomyces cerevisiae by Rad24-RFC (hRAD17-RFC), an alternate clamp loader in which Rad24 replaces Rfc1 in the RFC1-5 clamp loader of proliferating cell nuclear antigen (PCNA). The 9-1-1 clamp loading mechanism has been a mystery, because, unlike RFC, which loads PCNA onto a 3'-recessed junction, Rad24-RFC loads the 9-1-1 ring onto a 5'-recessed DNA junction. Here we report two cryo-EM structures of Rad24-RFC-DNA with a closed or 27-Å open 9-1-1 clamp. The structures reveal a completely unexpected mechanism by which a clamp can be loaded onto DNA. Unlike RFC, which encircles DNA, Rad24 binds 5'-DNA on its surface, not inside the loader, and threads the 3' ssDNA overhang into the 9-1-1 clamp from above the ring.

Indexed as

Cell Cycle ProteinsSaccharomyces cerevisiae ProteinsDNADNA ReplicationIntracellular Signaling Peptides and ProteinsProliferating Cell Nuclear AntigenReplication Protein CSaccharomyces cerevisiaeCell Cycle ProteinsDNAIntracellular Signaling Peptides and ProteinsProliferating Cell Nuclear AntigenRAD24 protein, S cerevisiaeReplication Protein CRFC1 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID35314830
PMCPMC9010301
OpenAlexW4220750365

What OpenQuestion holds

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Read underepoch 390

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.