Evidence map›Paper›PMID 32047031›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2020

Nucleolar localization of RAG1 modulates V(D)J recombination activity.

Ryan M Brecht, Catherine C Liu, Helen A Beilinson, Alexandra Khitun, Sarah A Slavoff, David G Schatz

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

24 citing papers in PubMed, 32 citations in OpenAlex.

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  15. Nemo-Dependent, ATM-Mediated Signals from RAG DNA Breaks atJournal of immunology (Baltimore, Md. : 1950) · 2022
    Article
  16. Review
  17. Nuclear Organization in Response to Stress: A Special Focus on Nucleoli.Results and problems in cell differentiation · 2022
    Article
  18. DNA Damage Response and Repair in Adaptive Immunity.Frontiers in cell and developmental biology · 2022
    Review
  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

6 authors at 1 institution in 1 country.

Ryan M BrechtDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06529.
Catherine C LiuDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06511.
Helen A BeilinsonDepartment of Immunobiology, Yale School of Medicine, New Haven, CT 06511.ORCID 0000-0002-2888-5256
Alexandra KhitunDepartment of Chemistry, Yale University, New Haven, CT 06520.
Sarah A SlavoffDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06529.
David G SchatzDepartment of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06529; david.schatz@yale.edu.ORCID 0000-0002-5669-1176
Yale University · US

Funding

Skill Development for Diverse Scientific Careers: A New Course Predoctoral Program in Cellular and Molecular BiologyT32GM007223 · NIGMS · YALE UNIVERSITY · PI BASERGA, SUSAN J · 1985 to 2019
$31.0M
INTERDISCIPLINARY IMMUNOLOGY TRAINING PROGRAMT32AI007019 · NIAID · YALE UNIVERSITY · PI Carrie L. Lucas, David G. Schatz · 1985 to 2026
$14.4M
Mechanism and Targeting of V(D)J RecombinationR01AI032524 · NIAID · YALE UNIVERSITY · PI David G. Schatz · 1992 to 2026
$6.7M
Structural and functional roles of the microprotein NoBody in mRNA decapping and decayR01GM122984 · NIGMS · YALE UNIVERSITY · PI SLAVOFF, SARAH ANN · 2017 to 2021
$1.6M
NIAID NIH HHS R01 AI032524NIAID NIH HHS T32 AI007019NIGMS NIH HHS R01 GM122984NIGMS NIH HHS T32 GM007223
6 · The paper itself

Abstract

V(D)J recombination assembles and diversifies Ig and T cell receptor genes in developing B and T lymphocytes. The reaction is initiated by the RAG1-RAG2 protein complex which binds and cleaves at discrete gene segments in the antigen receptor loci. To identify mechanisms that regulate V(D)J recombination, we used proximity-dependent biotin identification to analyze the interactomes of full-length and truncated forms of RAG1 in pre-B cells. This revealed an association of RAG1 with numerous nucleolar proteins in a manner dependent on amino acids 216 to 383 and allowed identification of a motif required for nucleolar localization. Experiments in transformed pre-B cell lines and cultured primary pre-B cells reveal a strong correlation between disruption of nucleoli, reduced association of RAG1 with a nucleolar marker, and increased V(D)J recombination activity. Mutation of the RAG1 nucleolar localization motif boosts recombination while removal of the first 215 amino acids of RAG1, required for efficient egress from nucleoli, reduces recombination activity. Our findings indicate that nucleolar sequestration of RAG1 is a negative regulatory mechanism in V(D)J recombination and identify regions of the RAG1 N-terminal region that control nucleolar association and egress.

Indexed as

V(D)J RecombinationAmino Acid MotifsAnimalsCell NucleolusCells, CulturedHomeodomain ProteinsMicePrecursor Cells, B-LymphoidProtein TransportHomeodomain ProteinsRAG-1 proteinB cell developmentnucleolusproximity-dependent biotin identificationRAG1V(D)J recombination

Identifiers

PMID32047031
PMCPMC7049140
OpenAlexW3006045793

What OpenQuestion holds

Textmetadata
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.