Evidence map›Paper›PMID 33398345›Full record

ArticleNucleic acids research2021

Catalytically inactive Cas9 impairs DNA replication fork progression to induce focal genomic instability.

Goro Doi, Satoshi Okada, Takehiro Yasukawa, Yuki Sugiyama, Siqin Bala, Shintaro Miyazaki, Dongchon Kang, Takashi Ito

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

36 citing papers in PubMed, 43 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
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  5. Article
  6. Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. DNA Polymerase Locks Replication Fork Under Stress.bioRxiv : the preprint server for biology · 2024
    Article
  15. Review
  16. Article
  17. Review
  18. CRISPR/Cas9 as a Mutagenic Factor.International journal of molecular sciences · 2024
    Review
  19. Modeling specific aneuploidies: from karyotype manipulations to biological insights.Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology · 2023
    Review
  20. Deletions of DNA in cancer and their possible uses for therapy.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023
    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

8 authors at 1 institution in 1 country.

Goro DoiDepartment of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Satoshi OkadaDepartment of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Takehiro YasukawaDepartment of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Yuki SugiyamaDepartment of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Siqin BalaDepartment of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Shintaro MiyazakiKyushu University School of Medicine, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Dongchon KangDepartment of Clinical Chemistry and Laboratory Medicine, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Takashi ItoDepartment of Biochemistry, Kyushu University Graduate School of Medical Sciences, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Kyushu University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Catalytically inactive Cas9 (dCas9) has become an increasingly popular tool for targeted gene activation/inactivation, live-cell imaging, and base editing. While dCas9 was reported to induce base substitutions and indels, it has not been associated with structural variations. Here, we show that dCas9 impedes replication fork progression to destabilize tandem repeats in budding yeast. When targeted to the CUP1 array comprising ∼16 repeat units, dCas9 induced its contraction in most cells, especially in the presence of nicotinamide. Replication intermediate analysis demonstrated replication fork stalling in the vicinity of dCas9-bound sites. Genetic analysis indicated that while destabilization is counteracted by the replisome progression complex components Ctf4 and Mrc1 and the accessory helicase Rrm3, it involves single-strand annealing by the recombination proteins Rad52 and Rad59. Although dCas9-mediated replication fork stalling is a potential risk in conventional applications, it may serve as a novel tool for both mechanistic studies and manipulation of genomic instability.

Indexed as

CRISPR-Cas SystemsDNA ReplicationGenomic InstabilityCRISPR-Associated Protein 9DNA Copy Number VariationsDNA, FungalDNA, Single-StrandedGene EditingGenes, FungalMetallothioneinMutagenesisNiacinamideRad52 DNA Repair and Recombination ProteinSaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsTandem Repeat SequencesCRISPR-Associated Protein 9CUP1-1 protein, S cerevisiaeDNA, FungalDNA, Single-StrandedMetallothioneinNiacinamideRad52 DNA Repair and Recombination ProteinRAD52 protein, S cerevisiaeSaccharomyces cerevisiae Proteins

Identifiers

PMID33398345
PMCPMC7826275
OpenAlexW3121004564

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.