Evidence map›Paper›PMID 25533186›Full record

ArticleMolecular cell2015

Yeast PP4 interacts with ATR homolog Ddc2-Mec1 and regulates checkpoint signaling.

Nicole Hustedt, Andrew Seeber, Ragna Sack, Monika Tsai-Pflugfelder, Bhupinder Bhullar, Hanneke Vlaming, Fred van Leeuwen, Aude Guénolé, Haico van Attikum, Rohith Srivas and 3 more

Open access · greenAbstract read
In one paragraph

Article in Molecular cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.3field-weighted citation impact, top 12% 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

36 citing papers in PubMed, 71 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. A DNA damage-induced phosphorylation circuit enhances Mec1Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  5. Article
  6. Article
  7. Article
  8. Review
  9. The Many Faces of Lipids in Genome Stability (and How to Unmask Them).International journal of molecular sciences · 2021
    Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Article
  15. Phospho-Regulation of Meiotic Prophase.Frontiers in cell and developmental biology · 2021
    Review
  16. Article
  17. Checkpoint Responses to DNA Double-Strand Breaks.Annual review of biochemistry · 2020
    Review
  18. Review
  19. 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

13 authors at 7 institutions in 3 countries.

Nicole HustedtFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
Andrew SeeberFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland.
Ragna SackFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Monika Tsai-PflugfelderFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Bhupinder BhullarNovartis Institutes for Biomedical Research, Novartis Pharma AG, Fabrikstrasse 22, 4056 Basel, Switzerland.
Hanneke VlamingDivision of Gene Regulation, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Fred van LeeuwenDivision of Gene Regulation, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, the Netherlands.
Aude GuénoléDepartment of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
Haico van AttikumDepartment of Toxicogenetics, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, the Netherlands.
Rohith SrivasDepartments of Bioengineering and Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Trey IdekerDepartments of Bioengineering and Medicine, University of California, San Diego, La Jolla, CA 92093, USA.
Kenji ShimadaFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland.
Susan M GasserFriedrich Miescher Institute for Biomedical Research, Maulbeerstrasse 66, 4058 Basel, Switzerland; Faculty of Sciences, University of Basel, 4056 Basel, Switzerland. Electronic address: susan.gasser@fmi.ch.
Friedrich Miescher Institute · CHLeiden University Medical Center · NLUniversity of California, San Diego · USNovartis (Switzerland) · CHOncode Institute · NLThe Netherlands Cancer Institute · NLUniversity of Basel · CH

Funding

A Systems Approach to Mapping the DNA Damage ResponseR01ES014811 · NIEHS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI IDEKER, TREY · 2005 to 2021
$8.6M
NIEHS NIH HHS R01 ES014811
6 · The paper itself

Abstract

Mec1-Ddc2 (ATR-ATRIP) controls the DNA damage checkpoint and shows differential cell-cycle regulation in yeast. To find regulators of Mec1-Ddc2, we exploited a mec1 mutant that retains catalytic activity in G2 and recruitment to stalled replication forks, but which is compromised for the intra-S phase checkpoint. Two screens, one for spontaneous survivors and an E-MAP screen for synthetic growth effects, identified loss of PP4 phosphatase, pph3Δ and psy2Δ, as the strongest suppressors of mec1-100 lethality on HU. Restored Rad53 phosphorylation accounts for part, but not all, of the pph3Δ-mediated survival. Phosphoproteomic analysis confirmed that 94% of the mec1-100-compromised targets on HU are PP4 regulated, including a phosphoacceptor site within Mec1 itself, mutation of which confers damage sensitivity. Physical interaction between Pph3 and Mec1, mediated by cofactors Psy2 and Ddc2, is shown biochemically and through FRET in subnuclear repair foci. This establishes a physical and functional Mec1-PP4 unit for regulating the checkpoint response.

Indexed as

Adaptor Proteins, Signal TransducingCell Cycle CheckpointsCell Cycle ProteinsCheckpoint Kinase 2DNA ReplicationEpistasis, GeneticGene Expression Regulation, FungalHEK293 CellsHumansIntracellular Signaling Peptides and ProteinsNuclear ProteinsPhosphoprotein PhosphatasesPhosphorylationProtein Processing, Post-TranslationalProtein Serine-Threonine KinasesSaccharomyces cerevisiaeAdaptor Proteins, Signal TransducingCell Cycle ProteinsCheckpoint Kinase 2Intracellular Signaling Peptides and ProteinsLCD1 protein, S cerevisiaeMEC1 protein, S cerevisiaeNuclear ProteinsPhosphoprotein PhosphatasesPPH3 protein, S cerevisiaeProtein Serine-Threonine KinasesPsy2 protein, S cerevisiaeRAD53 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID25533186
PMCPMC5706562
OpenAlexW1992359950

What OpenQuestion holds

Textmetadata
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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.