Evidence map›Paper›PMID 35701408›Full record

ArticleNature communications2022

Cas9-induced large deletions and small indels are controlled in a convergent fashion.

Michael Kosicki, Felicity Allen, Frances Steward, Kärt Tomberg, Yangyang Pan, Allan Bradley

Open access · goldAbstract read
In one paragraph

Article in Nature communications, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed
8.6field-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

80 citing papers in PubMed, 102 citations in OpenAlex.

  1. Generation ofJBMR plus · 2026
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  4. Establishment of CRISPR/Cas9 Genome Editing inJournal of fungi (Basel, Switzerland) · 2026
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  16. Evolution of Prime Editing: Enhancing Efficiency and Expanding Capacity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026
    Review
  17. Article
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  19. Article
  20. Review

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

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 3 institutions in 2 countries.

Michael KosickiLawrence Berkeley National Lab, Berkeley, CA, USA.
Felicity AllenWellcome Sanger Institute, Hinxton, UK.
Frances StewardThe Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
Kärt TombergThe Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.ORCID http://orcid.org/0000-0002-6144-3601
Yangyang PanThe Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK.
Allan BradleyThe Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Department of Medicine, University of Cambridge, Cambridge, UK. ab2592@cam.ac.uk.
University of Cambridge · GBLawrence Berkeley National Laboratory · USWellcome Sanger Institute · GB

Funding

Wellcome Trust 098051
6 · The paper itself

Abstract

Repair of Cas9-induced double-stranded breaks results primarily in formation of small insertions and deletions (indels), but can also cause potentially harmful large deletions. While mechanisms leading to the creation of small indels are relatively well understood, very little is known about the origins of large deletions. Using a library of clonal NGS-validated mouse embryonic stem cells deficient for 32 DNA repair genes, we have shown that large deletion frequency increases in cells impaired for non-homologous end joining and decreases in cells deficient for the central resection gene Nbn and the microhomology-mediated end joining gene Polq. Across deficient clones, increase in large deletion frequency was closely correlated with the increase in the extent of microhomology and the size of small indels, implying a continuity of repair processes across different genomic scales. Furthermore, by targeting diverse genomic sites, we identified examples of repair processes that were highly locus-specific, discovering a role for exonuclease Trex1. Finally, we present evidence that indel sizes increase with the overall efficiency of Cas9 mutagenesis. These findings may have impact on both basic research and clinical use of CRISPR-Cas9, in particular in conjunction with repair pathway modulation.

Indexed as

CRISPR-Cas SystemsDNA Breaks, Double-StrandedAnimalsDNA End-Joining RepairDNA RepairINDEL MutationMice

Identifiers

PMID35701408
PMCPMC9197861
OpenAlexW4282823317

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.