Evidence map›Paper›PMID 24753404›Full record

ArticleNucleic acids research2014

RAG2 mutants alter DSB repair pathway choice in vivo and illuminate the nature of 'alternative NHEJ'.

Vered Gigi, Susanna Lewis, Olga Shestova, Martina Mijušković, Ludovic Deriano, Wenzhao Meng, Eline T Luning Prak, David B Roth

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.

0numbers the graph read from it
0cells of the map it votes in
25citing papers in PubMed
3.1field-weighted citation impact, top 8% 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

25 citing papers in PubMed, 44 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
  5. DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022
    Review
  6. Review
  7. Review
  8. Article
  9. Ku70 suppresses alternative end joining in G1-arrested progenitor B cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. The ATM Kinase Restrains Joining of Both VDJ Signal and Coding Ends.Journal of immunology (Baltimore, Md. : 1950) · 2016
    Article
  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

8 authors at 3 institutions in 2 countries.

Vered GigiDepartment of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Susanna LewisDepartment of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Olga ShestovaDepartment of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Martina MijuškovićDepartment of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Ludovic DerianoDepartments of Immunology and Genomes & Genetics, Institut Pasteur, CNRS-URA 1961, 75015 Paris, France.
Wenzhao MengDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Eline T Luning PrakDepartment of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
David B RothDepartment of Pathology and Laboratory Medicine and Abramson Family Cancer Research Institute, Raymond and Ruth Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA david.roth2@uphs.upenn.edu.
Cancer Research Institute · USUniversity of Pennsylvania · USCentre National de la Recherche Scientifique · FR

Funding

RAG-induced DNA damage: mechanisms and responsesR01CA104588 · NCI · UNIVERSITY OF PENNSYLVANIA · PI ROTH, DAVID B. · 2004 to 2014
$2.8M
Chromosome translocation in pre B cells: the role of an alternate DNA structureR21AI097825 · NIAID · UNIVERSITY OF PENNSYLVANIA · PI LEWIS, SUSANNA MAXWELL · 2012 to 2013
$428k
NCI NIH HHS CA-104588NIAID NIH HHS 1R21AI097825-01
6 · The paper itself

Abstract

DNA double-stranded breaks (DSBs) can be repaired by several mechanisms, including classical NHEJ (c-NHEJ) and a poorly defined, error-prone process termed alternative NHEJ (a-NHEJ). How cells choose between these alternatives to join physiologic DSBs remains unknown. Here, we show that deletion of RAG2's C-terminus allows a-NHEJ to repair RAG-mediated DSBs in developing lymphocytes from both c-NHEJ-proficient and c-NHEJ-deficient mice, demonstrating that the V(D)J recombinase influences repair pathway choice in vivo. Analysis of V(D)J junctions revealed that, contrary to expectation, junctional characteristics alone do not reliably distinguish between a-NHEJ and c-NHEJ. These data suggest that a-NHEJ is not necessarily mutagenic, and may be more prevalent than previously appreciated. Whole genome sequencing of a lymphoma arising in a p53(-/-) mouse bearing a C-terminal RAG2 truncation reveals evidence of a-NHEJ and also of aberrant recognition of DNA sequences resembling RAG recognition sites.

Indexed as

DNA Breaks, Double-StrandedDNA End-Joining RepairAnimalsAntigens, NuclearDNA-Binding ProteinsGenes, p53Ku AutoantigenLymphomaMiceMice, KnockoutReceptors, Antigen, T-CellSequence DeletionTranslocation, GeneticV(D)J RecombinationAntigens, NuclearDNA-Binding ProteinsKu AutoantigenRag2 protein, mouseReceptors, Antigen, T-CellXrcc6 protein, mouse

Identifiers

PMID24753404
PMCPMC4041462
OpenAlexW2157088707

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.