Evidence map›Paper›PMID 26250113›Full record

ArticleNucleic acids research2015

A conserved Polϵ binding module in Ctf18-RFC is required for S-phase checkpoint activation downstream of Mec1.

Luis J García-Rodríguez, Giacomo De Piccoli, Vanessa Marchesi, Richard C Jones, Ricky D Edmondson, Karim Labib

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
3.6field-weighted citation impact, top 7% 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

39 citing papers in PubMed, 58 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. 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
  6. Article
  7. Article
  8. Article
  9. Smc5/6 Complex Promotes Rad3Molecular and cellular biology · 2022
    Article
  10. Review
  11. Global genomic instability caused by reduced expression of DNA polymerase ε in yeast.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Article
  17. Review
  18. Article
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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

6 authors at 5 institutions in 2 countries.

Luis J García-RodríguezCancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
Giacomo De PiccoliDivision of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Vanessa MarchesiCancer Research UK Manchester Institute, University of Manchester, Wilmslow Road, Manchester M20 4BX, UK.
Richard C JonesMS Bioworks, 3950 Varsity Drive, Ann Arbor, MI 48108, USA.
Ricky D EdmondsonMyeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, 4301 W Markham #776, Little Rock, AR 72205, USA.
Karim LabibMRC Protein Phosphorylation and Ubiquitylation Unit, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, UK kpmlabib@dundee.ac.uk.
Cancer Research UK Manchester Institute · GBBioWorks (United States) · USUniversity of Arkansas for Medical Sciences · USUniversity of Dundee · GBUniversity of Warwick · GB

Funding

Cancer Research UK 16326Cancer Research UK C44595/A16326Medical Research Council MC_UU_12016/13Wellcome Trust 097945/B/11/ZWellcome Trust 102943Wellcome Trust 102943/Z/13/Z
6 · The paper itself

Abstract

Defects during chromosome replication in eukaryotes activate a signaling pathway called the S-phase checkpoint, which produces a multifaceted response that preserves genome integrity at stalled DNA replication forks. Work with budding yeast showed that the 'alternative clamp loader' known as Ctf18-RFC acts by an unknown mechanism to activate the checkpoint kinase Rad53, which then mediates much of the checkpoint response. Here we show that budding yeast Ctf18-RFC associates with DNA polymerase epsilon, via an evolutionarily conserved 'Pol ϵ binding module' in Ctf18-RFC that is produced by interaction of the carboxyl terminus of Ctf18 with the Ctf8 and Dcc1 subunits. Mutations at the end of Ctf18 disrupt the integrity of the Pol ϵ binding module and block the S-phase checkpoint pathway, downstream of the Mec1 kinase that is the budding yeast orthologue of mammalian ATR. Similar defects in checkpoint activation are produced by mutations that displace Pol ϵ from the replisome. These findings indicate that the association of Ctf18-RFC with Pol ϵ at defective replication forks is a key step in activation of the S-phase checkpoint.

Indexed as

S Phase Cell Cycle CheckpointsDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA Polymerase IIDNA ReplicationHumansIntracellular Signaling Peptides and ProteinsMultienzyme ComplexesMutationProtein BindingProtein Serine-Threonine KinasesReplication Protein CReplisomesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsCTF18 protein, S cerevisiaeDcc1 protein, S cerevisiaeDNA-Binding ProteinsDNA-Directed DNA PolymeraseDNA Polymerase IIIntracellular Signaling Peptides and ProteinsMEC1 protein, S cerevisiaeMultienzyme ComplexesProtein Serine-Threonine KinasesReplication Protein CReplisomesSaccharomyces cerevisiae Proteins

Identifiers

PMID26250113
PMCPMC4605302
OpenAlexW1901491451

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Registered trials

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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.