Evidence map›Paper›PMID 32945578›Full record

ArticleThe EMBO journal2020

Structural basis for the activation and suppression of transposition during evolution of the RAG recombinase.

Yuhang Zhang, Elizabeth Corbett, Shenping Wu, David G Schatz

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 37% 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

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. How RAG1/2 evolved from ancestral transposases to initiate V(D)J recombination without transposition.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. 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

4 authors at 1 institution in 1 country.

Yuhang ZhangDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Elizabeth CorbettDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA.
Shenping WuDepartment of Pharmacology, Yale School of Medicine West Haven, New Haven, CT, USA.
David G SchatzDepartment of Immunobiology, Yale School of Medicine, New Haven, CT, USA.ORCID 0000-0002-5669-1176
Yale University · US

Funding

Function and Evolutionary Origins of the RAG EndonucleaseR01AI137079 · NIAID · YALE UNIVERSITY · PI David G. Schatz · 2018 to 2026
$5.1M
NIAID NIH HHS R01 AI137079
6 · The paper itself

Abstract

Jawed vertebrate adaptive immunity relies on the RAG1/RAG2 (RAG) recombinase, a domesticated transposase, for assembly of antigen receptor genes. Using an integration-activated form of RAG1 with methionine at residue 848 and cryo-electron microscopy, we determined structures that capture RAG engaged with transposon ends and U-shaped target DNA prior to integration (the target capture complex) and two forms of the RAG strand transfer complex that differ based on whether target site DNA is annealed or dynamic. Target site DNA base unstacking, flipping, and melting by RAG1 methionine 848 explain how this residue activates transposition, how RAG can stabilize sharp bends in target DNA, and why replacement of residue 848 by arginine during RAG domestication led to suppression of transposition activity. RAG2 extends a jawed vertebrate-specific loop to interact with target site DNA, and functional assays demonstrate that this loop represents another evolutionary adaptation acquired during RAG domestication to inhibit transposition. Our findings identify mechanistic principles of the final step in cut-and-paste transposition and the molecular and structural logic underlying the transformation of RAG from transposase to recombinase.

Indexed as

Evolution, MolecularAnimalsCryoelectron MicroscopyDNA-Binding ProteinsHMGB1 ProteinHomeodomain ProteinsHumansModels, MolecularNuclear ProteinsProtein ConformationRecombinasesRecombination, GeneticTransposasesVertebratesDNA-Binding ProteinsHMGB1 ProteinHMGB1 protein, humanHomeodomain ProteinsNuclear ProteinsRAG-1 proteinRAG2 protein, humanRecombinasesTransposasesDNA bendingevolutionrecombination-activating genetranspositionV(D)J recombination

Identifiers

PMID32945578
PMCPMC7604617
OpenAlexW3087609484

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.