Evidence map›Paper›PMID 24332808›Full record

ArticleMolecular cell2014

PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry.

Alexandre Maréchal, Ju-Mei Li, Xiao Ye Ji, Ching-Shyi Wu, Stephanie A Yazinski, Hai Dang Nguyen, Shizhou Liu, Amanda E Jiménez, Jianping Jin, Lee Zou

Open access · bronzeAbstract read
In one paragraph

Article in Molecular cell, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 161 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
161citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% 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

161 citing papers in PubMed, 1 synthesis or guideline pooled it, 240 citations in OpenAlex.

  1. Pooled it
  2. Genome stability disrupted by the circRBM39(4,5,6)-RPA2 axis represses breast tumorigenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  3. Article
  4. Review
  5. Review
  6. Article
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Increased PRP19 in Hepatocyte Impedes B Cell Function to Promote Hepatocarcinogenesis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024
    Article
  13. Article
  14. HeterozygousGenes & development · 2024
    Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

101 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 3 institutions in 1 country.

Alexandre MaréchalMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Ju-Mei Li *Department of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston Houston, TX 77030.
Xiao Ye Ji *Massachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Ching-Shyi WuMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Stephanie A YazinskiMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Hai Dang NguyenMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Shizhou LiuMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Amanda E JiménezMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Jianping JinDepartment of Biochemistry and Molecular Biology The University of Texas Health Science Center at Houston Houston, TX 77030.
Lee ZouMassachusetts General Hospital Cancer Center Harvard Medical School Charlestown, MA 02129.
Harvard University · USMassachusetts General Hospital · USThe University of Texas Health Science Center at Houston · US

Funding

Regulation of the ATR Checkpoint Kinase by DNA DamageR01GM076388 · NIGMS · MASSACHUSETTS GENERAL HOSPITAL · PI ZOU, LEE · 2006 to 2018
$4.3M
Post-ubiquitinational Regulation of I-kappa-B-alpha Proteolysis under StimuliR01GM102529 · NIGMS · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI JIN, JIANPING · 2012 to 2016
$1.4M
NCI NIH HHS BC120504NIGMS NIH HHS GM076388NIGMS NIH HHS GM102529NIGMS NIH HHS R01 GM076388NIGMS NIH HHS R01 GM102529
6 · The paper itself

Abstract

PRP19 is a ubiquitin ligase involved in pre-mRNA splicing and the DNA damage response (DDR). Although the role for PRP19 in splicing is well characterized, its role in the DDR remains elusive. Through a proteomic screen for proteins that interact with RPA-coated single-stranded DNA (RPA-ssDNA), we identified PRP19 as a sensor of DNA damage. PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. PRP19 facilitates the accumulation of ATRIP, the regulatory partner of the ataxia telangiectasia mutated and Rad3-related (ATR) kinase, at DNA damage sites. Depletion of PRP19 compromised the phosphorylation of ATR substrates, recovery of stalled replication forks, and progression of replication forks on damaged DNA. Importantly, PRP19 mutants that cannot bind RPA or function as an E3 ligase failed to support the ATR response, revealing that PRP19 drives ATR activation by acting as an RPA-ssDNA-sensing ubiquitin ligase during the DDR.

Indexed as

DNA DamageAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsCheckpoint Kinase 1DNA-Binding ProteinsDNA RepairDNA Repair EnzymesDNA ReplicationDNA, Single-StrandedHeLa CellsHumansNuclear ProteinsPhosphorylationProtein KinasesReplication Protein ARNA Splicing FactorsAdaptor Proteins, Signal TransducingAtaxia Telangiectasia Mutated ProteinsATRIP protein, humanATR protein, humanCheckpoint Kinase 1DNA-Binding ProteinsDNA Repair EnzymesDNA, Single-StrandedNuclear ProteinsProtein KinasesPRPF19 protein, humanReplication Protein ARNA Splicing FactorsUbiquitin

Identifiers

PMID24332808
PMCPMC3946837
OpenAlexW2082078734

What OpenQuestion holds

Textmetadata
LicenceTDM
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.