Evidence map›Paper›PMID 25707795›Full record

ArticleNature2015

Integrase-mediated spacer acquisition during CRISPR-Cas adaptive immunity.

James K Nuñez, Amy S Y Lee, Alan Engelman, Jennifer A Doudna

Open access · greenAbstract read
In one paragraph

Article in Nature, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 217 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
217citing papers in PubMed, 1 pooled it
22.9field-weighted citation impact, top 1% 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

217 citing papers in PubMed, 1 synthesis or guideline pooled it, 356 citations in OpenAlex.

  1. Engineering CRISPR guide RNAs for programmable RNA sensors.Biochemical Society transactions · 2023
    Pooled it
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Structural characterization of anti-CRISPR protein AcrIE9.Structural dynamics (Melville, N.Y.) · 2025
    Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. CRISPR-Cas Systems: A Functional Perspective and Innovations.International journal of molecular sciences · 2025
    Review
  16. Article
  17. Article
  18. CRISPR and gene editing technologies for bleeding disorders.Therapeutic advances in hematology · 2025
    Review
  19. Article
  20. Review

157 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

James K NuñezDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Amy S Y Lee1] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Center for RNA Systems Biology, University of California, Berkeley, Berkeley, California 94720, USA.
Alan EngelmanDepartment of Cancer Immunology and AIDS, Dana-Farber Cancer Institute and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA.
Jennifer A Doudna1] Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA [2] Center for RNA Systems Biology, University of California, Berkeley, Berkeley, California 94720, USA [3] Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, California 94720, USA [4] Department of Chemistry, University of California, Berkeley, Berkeley, California 94720, USA [5] Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
University of California, Berkeley · USHarvard University · US

Funding

Univ of Calif Berkeley Chemistry-Biology Interface ProgramT32GM066698 · NIGMS · UNIVERSITY OF CALIFORNIA BERKELEY · PI CHANG, CHRISTOPHER J., FRANCIS, MATTHEW B · 2004 to 2023
$7.5M
Integrase Structural VirologyR01AI070042 · NIAID · DANA-FARBER CANCER INST · PI ENGELMAN, ALAN N. · 2006 to 2020
$7.2M
Genome Sequencer FLXS10RR029668 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI NGAI, JOHN J. · 2010 to 2010
$623k
Illumina Sequencer to Facilitate Functional Genomics at BerkeleyS10RR027303 · NCRR · UNIVERSITY OF CALIFORNIA BERKELEY · PI TAYLOR, JOHN W. · 2010 to 2010
$500k
Howard Hughes Medical InstituteNCRR NIH HHS S10 RR027303NCRR NIH HHS S10RR027303NCRR NIH HHS S10 RR029668NCRR NIH HHS S10RR029668NIAID NIH HHS AI070042NIAID NIH HHS R01 AI070042NIGMS NIH HHS T32 GM066698
6 · The paper itself

Abstract

Bacteria and archaea insert spacer sequences acquired from foreign DNAs into CRISPR loci to generate immunological memory. The Escherichia coli Cas1-Cas2 complex mediates spacer acquisition in vivo, but the molecular mechanism of this process is unknown. Here we show that the purified Cas1-Cas2 complex integrates oligonucleotide DNA substrates into acceptor DNA to yield products similar to those generated by retroviral integrases and transposases. Cas1 is the catalytic subunit and Cas2 substantially increases integration activity. Protospacer DNA with free 3'-OH ends and supercoiled target DNA are required, and integration occurs preferentially at the ends of CRISPR repeats and at sequences adjacent to cruciform structures abutting AT-rich regions, similar to the CRISPR leader sequence. Our results demonstrate the Cas1-Cas2 complex to be the minimal machinery that catalyses spacer DNA acquisition and explain the significance of CRISPR repeats in providing sequence and structural specificity for Cas1-Cas2-mediated adaptive immunity.

Indexed as

Adaptive ImmunityAT Rich SequenceClustered Regularly Interspaced Short Palindromic RepeatsCRISPR-Associated ProteinsCRISPR-Cas SystemsDNADNA, SuperhelicalEscherichia coliIntegrasesNucleic Acid ConformationSubstrate SpecificityTransposasesCRISPR-Associated ProteinsDNADNA, SuperhelicalIntegrasesTransposases

Identifiers

PMID25707795
PMCPMC4359072
OpenAlexW2164807693

What OpenQuestion holds

Textmetadata
LicenceTDM
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.