Evidence map›Paper›PMID 33764556›Full record

ArticleThe EMBO journal2021

Phosphoproteomics reveals a distinctive Mec1/ATR signaling response upon DNA end hyper-resection.

Ethan J Sanford, William J Comstock, Vitor M Faça, Stephanie C Vega, Robert Gnügge, Lorraine S Symington, Marcus B Smolka

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

16 citing papers in PubMed, 28 citations in OpenAlex.

  1. DNA Damage and Replication Stress Checkpoints.Annual review of biochemistry · 2025
    Review
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. A DNA damage-induced phosphorylation circuit enhances Mec1Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article
  9. International journal of molecular sciences · 2022
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Article
  15. DNA damage checkpoint and repair: From the budding yeastComputational and structural biotechnology journal · 2021
    Review
  16. 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

7 authors at 3 institutions in 2 countries.

Ethan J SanfordDepartment of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.ORCID 0000-0003-0722-3058
William J ComstockDepartment of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Vitor M FaçaDepartment of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Stephanie C VegaDepartment of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.
Robert GnüggeDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
Lorraine S SymingtonDepartment of Microbiology and Immunology, Columbia University Irving Medical Center, New York, NY, USA.
Marcus B SmolkaDepartment of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, NY, USA.ORCID 0000-0001-9952-2885
Cornell University · USColumbia University Irving Medical Center · USUniversidade de São Paulo · BR

Funding

Mechanism and regulation of DNA double-strand break repairR35GM126997 · NIGMS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Lorraine S Symington · 2018 to 2026
$5.9M
Signaling Mechanisms in Genome Maintenance (Equipment Supplement 2023)R35GM141159 · NIGMS · CORNELL UNIVERSITY · PI Marcus Smolka · 2021 to 2026
$3.5M
Cellular Responses to DNA Replication StressR01GM097272 · NIGMS · CORNELL UNIVERSITY · PI SMOLKA, MARCUS · 2011 to 2020
$2.7M
NIGMS NIH HHS R01 GM097272NIGMS NIH HHS R35 GM126997NIGMS NIH HHS R35 GM141159
6 · The paper itself

Abstract

The Mec1/ATR kinase is crucial for genome maintenance in response to a range of genotoxic insults, but it remains unclear how it promotes context-dependent signaling and DNA repair. Using phosphoproteomic analyses, we uncovered a distinctive Mec1/ATR signaling response triggered by extensive nucleolytic processing (resection) of DNA ends. Budding yeast cells lacking Rad9, a checkpoint adaptor and an inhibitor of resection, exhibit a selective increase in Mec1-dependent phosphorylation of proteins associated with single-strand DNA (ssDNA) transactions, including the ssDNA-binding protein Rfa2, the translocase/ubiquitin ligase Uls1, and the Sgs1-Top3-Rmi1 (STR) complex that regulates homologous recombination (HR). Extensive Mec1-dependent phosphorylation of the STR complex, mostly on the Sgs1 helicase subunit, promotes an interaction between STR and the DNA repair scaffolding protein Dpb11. Fusion of Sgs1 to phosphopeptide-binding domains of Dpb11 strongly impairs HR-mediated repair, supporting a model whereby Mec1 signaling regulates STR upon hyper-resection to influence recombination outcomes. Overall, the identification of a distinct Mec1 signaling response triggered by hyper-resection highlights the multi-faceted action of this kinase in the coordination of checkpoint signaling and HR-mediated DNA repair.

Indexed as

Cell Cycle ProteinsDNA RepairHomologous RecombinationIntracellular Signaling Peptides and ProteinsProtein Serine-Threonine KinasesRecQ HelicasesSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSignal TransductionCell Cycle ProteinsDPB11 protein, S cerevisiaeIntracellular Signaling Peptides and ProteinsMEC1 protein, S cerevisiaeProtein Serine-Threonine KinasesRecQ HelicasesSaccharomyces cerevisiae ProteinsSGS1 protein, S cerevisiaeDpb11homologous recombinationMec1resectionSgs1

Identifiers

PMID33764556
PMCPMC8126923
OpenAlexW3139214630

What OpenQuestion holds

Textmetadata
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.