Evidence map›Paper›PMID 32704141›Full record

ArticleScientific reports2020

DNA unchained: two assays to discover and study inhibitors of the DNA clustering function of barrier-to-autointegration factor.

Michael Burger, Caroline Schmitt-Koopmann, Jean-Christophe Leroux

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
1.6field-weighted citation impact, top 16% 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

12 citing papers in PubMed, 16 citations in OpenAlex.

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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

3 authors at 1 institution in 1 country.

Michael BurgerInstitute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Caroline Schmitt-KoopmannInstitute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland.
Jean-Christophe LerouxInstitute of Pharmaceutical Sciences, ETH Zurich, Zurich, Switzerland. jleroux@ethz.ch.
ETH Zurich · CH

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The protein barrier-to-autointegration factor (BAF) and its interaction partners, the LEM (LAP2B, emerin, MAN1)-domain proteins, constitute a powerful cytoplasmic DNA defense mechanism. Invading DNA molecules are quickly bound by the BAF system and trapped in membrane compartments. This decreases the nuclear uptake of DNA from the cytoplasm. Inhibition of the BAF system is therefore expected to enhance the efficacy of non-viral DNA transfection agents. In this study, we introduced a protocol for the recombinant expression of soluble BAF and developed two ELISA-type assays to discover small molecule inhibitors of BAF-dependent DNA retention by high throughput screening (HTS). The proton pump inhibitor rabeprazole as well as three compounds of the Maybridge library were identified as inhibitors of the LEM-BAF-DNA interaction chain. The inhibition was based on adduct formation with BAF cysteine residues. An enhancing effect of the compounds on cell culture transfection, however, was not observed, which may be attributed to the reducing environment of the cytoplasm that prevents the adduct formation with BAF cysteine residues. The novel assays developed here can provide new tools to further study the biological functions of the BAF system, and may lead to the identification of suitable BAF inhibitors in future HTS campaigns.

Indexed as

High-Throughput Screening AssaysDNADNA-Binding ProteinsHeLa CellsHumansMembrane ProteinsNuclear ProteinsRabeprazoleReproducibility of ResultsSmall Molecule LibrariesBANF1 protein, humanDNADNA-Binding ProteinsemerinMembrane ProteinsNuclear ProteinsRabeprazoleSmall Molecule Libraries

Identifiers

PMID32704141
PMCPMC7378220
OpenAlexW3044385079

What OpenQuestion holds

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LicenceCC BY
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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.