Evidence map›Paper›PMID 27643854›Full record

ArticlePloS one2016

Chemical Inhibitors of Non-Homologous End Joining Increase Targeted Construct Integration in Cryptococcus neoformans.

Samantha D M Arras, James A Fraser

Abstract read
In one paragraph

Article in PloS one, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
–field-weighted citation impact
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

20 citing papers in PubMed.

  1. CRISPR Gene Tagging for Illuminating Endogenous Protein Dynamics.International journal of molecular sciences · 2026
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  6. A Chimeric ORF Fusion Phenotypic Reporter forJournal of fungi (Basel, Switzerland) · 2024
    Article
  7. Review
  8. Article
  9. Article
  10. Variation amongMicroorganisms · 2021
    Article
  11. Article
  12. Article
  13. Article
  14. Review
  15. Overexpression ofMicroorganisms · 2019
    Article
  16. Review
  17. Article
  18. Article
  19. Control of gene editing by manipulation of DNA repair mechanisms.Mammalian genome : official journal of the International Mammalian Genome Society · 2017
    Review
  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

2 authors.

Samantha D M ArrasAustralian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072 Australia.
James A FraserAustralian Infectious Diseases Research Centre, School of Chemistry & Molecular Biosciences, The University of Queensland, St Lucia, QLD 4072 Australia.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The development of a biolistic transformation protocol for Cryptococcus neoformans over 25 years ago ushered in a new era of molecular characterization of virulence in this previously intractable fungal pathogen. However, due to the low rate of homologous recombination in this species, the process of creating targeted gene deletions using biolistic transformation remains inefficient. To overcome the corresponding difficulty achieving molecular genetic modifications, members of the Cryptococcus community have investigated the use of specific genetic backgrounds or construct design strategies aimed at reducing ectopic construct integration via non-homologous end joining (NHEJ). One such approach involves deletion of components of the NHEJ-associated Ku heterodimer. While this strategy increases homologous recombination to nearly 100%, it also restricts strain generation to a ku80Δ genetic background and requires subsequent complex mating procedures to reestablish wild-type DNA repair. In this study, we have investigated the ability of known inhibitors of mammalian NHEJ to transiently phenocopy the C. neoformans Ku deletion strains. Testing of eight candidate inhibitors revealed a range of efficacies in C. neoformans, with the most promising compound (W7) routinely increasing the rate of gene deletion to over 50%. We have successfully employed multiple inhibitors to reproducibly enhance the deletion rate at multiple loci, demonstrating a new, easily applied methodology to expedite acquisition of precise genetic alterations in C. neoformans. Based on this success, we anticipate that the use of these inhibitors will not only become widespread in the Cryptococcus community, but may also find use in other fungal species as well.

Indexed as

Cryptococcus neoformansDNA DamageDNA End-Joining RepairGene DeletionGenes, FungalVirulence

Identifiers

PMID27643854
PMCPMC5028063

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Registered trials

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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.