Evidence map›Paper›PMID 26474068›Full record

ArticleMolecular cell2015

RFWD3-Dependent Ubiquitination of RPA Regulates Repair at Stalled Replication Forks.

Andrew E H Elia, David C Wang, Nicholas A Willis, Alexander P Boardman, Ildiko Hajdu, Richard O Adeyemi, Elizabeth Lowry, Steven P Gygi, Ralph Scully, Stephen J Elledge

Abstract 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 94 papers.

0numbers the graph read from it
0cells of the map it votes in
94citing papers in PubMed
4.7field-weighted citation impact, top 4% 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

94 citing papers in PubMed, 132 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Targeting ubiquitination in disease and therapy.Signal transduction and targeted therapy · 2025
    Review
  6. Article
  7. Article
  8. Article
  9. Article
  10. HeterozygousGenes & development · 2024
    Article
  11. Review
  12. Article
  13. Review
  14. Article
  15. Review
  16. Review
  17. Article
  18. Article
  19. MicroRNA-190b Targets RFWD3 in Estrogen Receptor-Positive Breast Cancer.Breast cancer : basic and clinical research · 2024
    Article
  20. Review

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

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 4 institutions in 1 country.

Andrew E H EliaDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
David C WangDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Nicholas A WillisDepartment of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Alexander P BoardmanDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Ildiko HajduDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA.
Richard O AdeyemiDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA.
Elizabeth LowryDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA; Department of Radiation Oncology, Massachusetts General Hospital, Boston, MA 02114, USA.
Steven P GygiDepartment of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Ralph ScullyDepartment of Medicine and Cancer Research Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Stephen J ElledgeDepartment of Genetics, Harvard Medical School; Division of Genetics, Brigham and Women's Hospital; Howard Hughes Medical Institute, Boston, MA 02115, USA. Electronic address: selledge@genetics.med.harvard.edu.
Brigham and Women's Hospital · USCancer Research Institute · USHarvard University · USHoward Hughes Medical Institute · US

Funding

Dana Farber/Harvard Cancer Consortium Career Development Program in Clinical OncologyK12CA087723 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI David Tsai Ting · 2002 to 2026
$17.9M
Ubiquitin Mediated Proteolysis and Cell Cycle ControlR01AG011085 · NIA · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI JEFFREY W HARPER · 1993 to 2026
$10.9M
New Sample Multiplexing Technologies to Identify Chemical Probes and Illuminate Ubiquitin BiologyR01GM067945 · NIGMS · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI GYGI, STEVEN P · 2003 to 2024
$10.5M
ANALYSIS OF BRCA1 RECOMBINATION FUNCTIONSR01CA095175 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCULLY, RALPH · 2002 to 2021
$4.9M
The chromatin response in mammalian double strand break repairR01GM073894 · NIGMS · BETH ISRAEL DEACONESS MEDICAL CENTER · PI SCULLY, RALPH · 2005 to 2014
$2.5M
GENETICS OF CELL CYCLE &DNA DAMAGE REGULATION IN YEASTR01GM044664 · NIGMS · BRIGHAM AND WOMEN'S HOSPITAL · PI ELLEDGE, STEPHEN J · 1990 to 2016
$2.0M
Howard Hughes Medical InstituteNCI NIH HHS K12 CA087723NCI NIH HHS R01 CA095175NIA NIH HHS R01 AG011085NIGMS NIH HHS R01 GM044664NIGMS NIH HHS R01 GM067945NIGMS NIH HHS R01 GM073894
6 · The paper itself

Abstract

We have used quantitative proteomics to profile ubiquitination in the DNA damage response (DDR). We demonstrate that RPA, which functions as a protein scaffold in the replication stress response, is multiply ubiquitinated upon replication fork stalling. Ubiquitination of RPA occurs on chromatin, involves sites outside its DNA binding channel, does not cause proteasomal degradation, and increases under conditions of fork collapse, suggesting a role in repair at stalled forks. We demonstrate that the E3 ligase RFWD3 mediates RPA ubiquitination. RFWD3 is necessary for replication fork restart, normal repair kinetics during replication stress, and homologous recombination (HR) at stalled replication forks. Mutational analysis suggests that multisite ubiquitination of the entire RPA complex is responsible for repair at stalled forks. Multisite protein group sumoylation is known to promote HR in yeast. Our findings reveal a similar requirement for multisite protein group ubiquitination during HR at stalled forks in mammalian cells.

Indexed as

DNA RepairDNA ReplicationChromatinDNADNA DamageHeLa CellsHomologous RecombinationHumansModels, MolecularMutationProtein BindingProtein SubunitsReplication Protein AUbiquitinationUbiquitin-Protein LigasesChromatinDNAProtein SubunitsReplication Protein ARFWD3 protein, humanUbiquitin-Protein Ligases

Identifiers

PMID26474068
PMCPMC4609029
OpenAlexW2126788133

What OpenQuestion holds

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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.