Evidence map›Paper›PMID 28179379›Full record

ArticleThe Journal of experimental medicine2017

RAG1/2 induces genomic insertions by mobilizing DNA into RAG1/2-independent breaks.

Philipp C Rommel, Thiago Y Oliveira, Michel C Nussenzweig, Davide F Robbiani

Erratum issuedOpen access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
0.7field-weighted citation impact, top 34% 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

14 citing papers in PubMed, 24 citations in OpenAlex.

  1. Review
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Different classes of genomic inserts contribute to human antibody diversity.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  8. Review
  9. Review
  10. MiRAGDB: A Knowledgebase of RAG Regulators.Frontiers in immunology · 2022
    Article
  11. Article
  12. Article
  13. Review
  14. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Philipp C RommelLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-9790-4086
Thiago Y OliveiraLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065.ORCID 0000-0002-2654-0879
Michel C NussenzweigLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 drobbiani@rockefeller.edu nussen@rockefeller.edu.ORCID 0000-0003-0592-8564
Davide F RobbianiLaboratory of Molecular Immunology, The Rockefeller University, New York, NY 10065 drobbiani@rockefeller.edu nussen@rockefeller.edu.ORCID 0000-0001-7379-3484
Rockefeller University · USHoward Hughes Medical Institute · US

Funding

Class Switch Recombination in B LymphocytesR37AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2014 to 2023
$5.4M
SIGNALLING PATHWAYS IN AUTOIMMUNITYR01AI037526 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 1994 to 2012
$5.0M
Cellular dynamics in germinal centers during vaccinationR01AI072529 · NIAID · ROCKEFELLER UNIVERSITY · PI NUSSENZWEIG, MICHEL C · 2007 to 2016
$4.3M
Chromosome fragility and translocations in lymphocytesR21AI112602 · NIAID · ROCKEFELLER UNIVERSITY · PI ROBBIANI, DAVIDE FILIPPO · 2015 to 2016
$466k
Cancer Research UKHoward Hughes Medical InstituteNIAID NIH HHS R01 AI037526NIAID NIH HHS R01 AI072529NIAID NIH HHS R21 AI112602NIAID NIH HHS R37 AI037526
6 · The paper itself

Abstract

The RAG recombinase (RAG1/2) plays an essential role in adaptive immunity by mediating V(D)J recombination in developing lymphocytes. In contrast, aberrant RAG1/2 activity promotes lymphocyte malignancies by causing chromosomal translocations and DNA deletions at cancer genes. RAG1/2 can also induce genomic DNA insertions by transposition and trans-V(D)J recombination, but only few such putative events have been documented in vivo. We used next-generation sequencing techniques to examine chromosomal rearrangements in primary murine B cells and discovered that RAG1/2 causes aberrant insertions by releasing cleaved antibody gene fragments that subsequently reintegrate into DNA breaks induced on a heterologous chromosome. We confirmed that RAG1/2 also mobilizes genomic DNA into independent physiological breaks by identifying similar insertions in human lymphoma and leukemia. Our findings reveal a novel RAG1/2-mediated insertion pathway distinct from DNA transposition and trans-V(D)J recombination that destabilizes the genome and shares features with reported oncogenic DNA insertions.

Indexed as

DNA DamageMutagenesis, InsertionalAnimalsB-LymphocytesDNA-Binding ProteinsGenomic InstabilityHomeodomain ProteinsImmunoglobulinsMiceMice, Inbred C57BLReceptors, Antigen, T-CellTranslocation, GeneticV(D)J RecombinationDNA-Binding ProteinsHomeodomain ProteinsIgKImmunoglobulinsRAG-1 proteinRag2 protein, mouseReceptors, Antigen, T-Cell

Identifiers

PMID28179379
PMCPMC5339680
OpenAlexW2586897381

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
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.