Evidence map›Paper›PMID 31875554›Full record

ArticleCell reports2019

Intra-Vκ Cluster Recombination Shapes the Ig Kappa Locus Repertoire.

Kenta Shinoda, Yaakov Maman, Andres Canela, David G Schatz, Ferenc Livak, André Nussenzweig

Abstract read
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
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

9 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks atJournal of immunology (Baltimore, Md. : 1950) · 2022
    Article
  7. Article
  8. Review
  9. Genome Topology Control of Antigen Receptor Gene Assembly.Journal of immunology (Baltimore, Md. : 1950) · 2020
    Review
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

6 authors.

Kenta ShinodaLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA.
Yaakov MamanLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA; The Azrieli Faculty of Medicine, Bar-Ilan University, Safed, Israel.
Andres CanelaLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA; The Hakubi Center for Advanced Research and Radiation Biology Center, Graduate School of Biostudies, Kyoto University, Kyoto, Japan.
David G SchatzDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Ferenc LivakLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA. Electronic address: ferenc.livak@nih.gov.
André NussenzweigLaboratory of Genome Integrity, National Cancer Institute, NIH, Bethesda, MD, USA. Electronic address: andre_nussenzweig@nih.gov.

Funding

CCR, LGI, Flow Cytometry Core FacilityZICBC011428 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI LIVAK, FERENC · 2012 to 2025
$17.3M
Mechanism and Targeting of V(D)J RecombinationR01AI032524 · NIAID · YALE UNIVERSITY · PI David G. Schatz · 1992 to 2026
$6.7M
DNA REPAIRZ01BC010283 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 1998 to 2008
$2.9M
Relationship between DNA damage detection and signalingZ01BC010959 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSENZWEIG, ANDRE A. · 2008 to 2008
$812k
Intramural NIH HHS Z01 BC010283Intramural NIH HHS Z01 BC010959Intramural NIH HHS ZIC BC011428NIAID NIH HHS R01 AI032524
6 · The paper itself

Abstract

During V(D)J recombination, RAG proteins introduce DNA double-strand breaks (DSBs) at recombination signal sequences (RSSs) that contain either 12- or 23-nt spacer regions. Coordinated 12/23 cleavage predicts that DSBs at variable (V) gene segments should equal the level of breakage at joining (J) segments. Contrary to this, here we report abundant RAG-dependent DSBs at multiple Vκ gene segments independent of V-J rearrangement. We find that a large fraction of Vκ gene segments are flanked not only by a bone-fide 12 spacer but also an overlapping, 23-spacer flipped RSS. These compatible pairs of RSSs mediate recombination and deletion inside the Vκ cluster even in the complete absence of Jκ gene segments and support a V(D)J recombination center (RC) independent of the conventional Jκ-centered RC. We propose an improved model of Vκ-Jκ repertoire formation by incorporating these surprisingly frequent, evolutionarily conserved intra-Vκ cluster recombination events.

Indexed as

AnimalsB-LymphocytesClone CellsCRISPR-Cas SystemsDNADNA Breaks, Double-StrandedDNA Ligase ATPEndonucleasesFemaleGene EditingHomeodomain ProteinsImmunoglobulin Variable RegionMaleMiceMice, Inbred C57BLMice, TransgenicDclre1c protein, mouseDNADNA Ligase ATPEndonucleasesHomeodomain ProteinsImmunoglobulin Variable RegionLig4 protein, mouseNuclear ProteinsRAG-1 proteinEND-seqHTGTSig kappa locusig repertoireimmunoglobulinRAGrecombination centerrecombination signal sequencevariableVDJ recombination

Identifiers

PMID31875554
PMCPMC8214342

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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.