Evidence map›Paper›PMID 25833945›Full record

ArticleThe Journal of biological chemistry2015

14-3-3 proteins restrain the Exo1 nuclease to prevent overresection.

Xiaoqing Chen, In-Kwon Kim, Yuchi Honaker, Sharad C Paudyal, Won Kyun Koh, Melanie Sparks, Shan Li, Helen Piwnica-Worms, Tom Ellenberger, Zhongsheng You

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 1 pooled it
1.5field-weighted citation impact, top 18% 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

22 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Deciphering the multifaceted role ofFrontiers in immunology · 2025
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  5. Article
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  7. TCAF1 promotes TRPV2-mediated CaNature communications · 2024
    Article
  8. Article
  9. ATM controls the extent of DNA end resection by eliciting sequential posttranslational modifications of CtIP.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Specific Human ATR and ATM Inhibitors Modulate Single Strand DNA Formation inFrontiers in cellular and infection microbiology · 2021
    Article
  11. Article
  12. Review
  13. Article
  14. Journal of Cancer · 2020
    Article
  15. CaMolecular cell · 2019
    Article
  16. Article
  17. Review
  18. Review
  19. Article
  20. 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

10 authors at 1 institution in 1 country.

Xiaoqing ChenFrom the Departments of Cell Biology and Physiology and.
In-Kwon KimBiochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110 and.
Yuchi HonakerFrom the Departments of Cell Biology and Physiology and.
Sharad C PaudyalFrom the Departments of Cell Biology and Physiology and.
Won Kyun KohFrom the Departments of Cell Biology and Physiology and.
Melanie SparksFrom the Departments of Cell Biology and Physiology and.
Shan LiFrom the Departments of Cell Biology and Physiology and.
Helen Piwnica-WormsFrom the Departments of Cell Biology and Physiology and the Department of Cancer Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77230.
Tom EllenbergerBiochemistry and Molecular Biophysics, Washington University School of Medicine, St. Louis, Missouri 63110 and.
Zhongsheng YouFrom the Departments of Cell Biology and Physiology and zyou@wustl.edu.
Washington University in St. Louis · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
MOLECULAR ONCOLOGY TRAINING GRANTT32CA113275 · NCI · WASHINGTON UNIVERSITY · PI Matthew J Walter · 2006 to 2026
$5.7M
MOLECULAR MECHANISMS OF DNA DAMAGE SIGNALING AND REPAIRR01GM098535 · NIGMS · WASHINGTON UNIVERSITY · PI PISTON, DAVID W · 2012 to 2025
$4.2M
NCI NIH HHS P01 CA092584NCI NIH HHS P01CA92584NCI NIH HHS T32 CA113275NIGMS NIH HHS R01 GM098535NIGMS NIH HHS R01GM098535
6 · The paper itself

Abstract

The DNA end resection process dictates the cellular response to DNA double strand break damage and is essential for genome maintenance. Although insufficient DNA resection hinders homology-directed repair and ATR (ataxia telangiectasia and Rad3 related)-dependent checkpoint activation, overresection produces excessive single-stranded DNA that could lead to genomic instability. However, the mechanisms controlling DNA end resection are poorly understood. Here we show that the major resection nuclease Exo1 is regulated both positively and negatively by protein-protein interactions to ensure a proper level of DNA resection. We have shown previously that the sliding DNA clamp proliferating cell nuclear antigen (PCNA) associates with the C-terminal domain of Exo1 and promotes Exo1 damage association and DNA resection. In this report, we show that 14-3-3 proteins interact with a central region of Exo1 and negatively regulate Exo1 damage recruitment and subsequent resection. 14-3-3s limit Exo1 damage association, at least in part, by suppressing its association with PCNA. Disruption of the Exo1 interaction with 14-3-3 proteins results in elevated sensitivity of cells to DNA damage. Unlike Exo1, the Dna2 resection pathway is apparently not regulated by PCNA and 14-3-3s. Our results provide critical insights into the mechanism and regulation of the DNA end resection process and may have implications for cancer treatment.

Indexed as

DNA Breaks, Double-StrandedGene Expression Regulation14-3-3 ProteinsAnimalsCell Line, TumorCell NucleusCell SurvivalDNADNA RepairExodeoxyribonucleasesGlutathione TransferaseGreen Fluorescent ProteinsHEK293 CellsHumansMicroscopy, FluorescenceMutation14-3-3 ProteinsDNAexodeoxyribonuclease IExodeoxyribonucleasesGlutathione TransferaseGreen Fluorescent ProteinsProliferating Cell Nuclear AntigenRecombinant Proteins14-3-3 proteincheckpoint controlDNA damage responseDNA repairDNA resectionExo1proliferating cell nuclear antigen (PCNA)

Identifiers

PMID25833945
PMCPMC4424361
OpenAlexW1972471442

What Socratic 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 Socratic graph.