dictyNews
Electronic Edition
Volume 45, number 11
April 7, 2019
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Abstracts
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Advice on avoiding the Valley of Death: Insights from a 3Rs model
of aversive and emetic compound identification
Robin S.B. Williams and Paul L.R. Andrews
ALTEX https://www.altex.org/index.php/altex/article/view/1177
The gap between the development of new 3Rs (replace, reduce, refine)
technologies and their implementation into routine use has been called
the “Valley of Death”. Reasons for reluctance in adoption of these
approaches, particularly by industry, are often complex, and may be
related to a lack of awareness of, or confidence in, 3Rs approaches.
We report from the Valley of Death, on a long-term project developing
the social amoeba Dictyostelium discoideum as an innovative 3Rs
alternative to the use of animals for early identification of novel chemical
entities (NCEs) with aversive and emetic properties, to provide guidance
so others may learn from our experience.
submitted by: Robin Wiliams [[log in to unmask]]
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Mapping and characterization of G-quadruplexes in the genome
of the social amoeba Dictyostelium
discoideum
Saad M, Guédin A, Amor S, Bedrat A, Tourasse NJ,
Fayyad-Kazan H, Pratviel G, Lacroix L, Mergny JL
Nucleic Acids Res., in press
G-quadruplexes (G4) are non-canonical DNA and/or RNA secondary
structures formed in guanine-rich regions. Given their over-representation
in specific regions in the genome such as promoters and telomeres, they
are likely to play important roles in key processes such as transcription,
replication or RNA maturation. Putative G4-forming sequences (G4FS)
have been reported in humans, yeast, bacteria, viruses and many organisms.
Here we present the first mapping of G-quadruplex sequences in Dictyostelium
discoideum, the social amoeba. ‘Dicty’ is an ameboid protozoan with a small
(34 Mb) and extremely AT rich genome (78%). As a consequence, very few
G4-prone motifs are expected. An in silico analysis of the Dictyostelium genome
with the G4Hunter software detected 249–1055 G4-prone motifs, depending on
G4Hunter chosen threshold. Interestingly, despite an even lower GC content
(as compared to the whole Dicty genome), the density of G4 motifs in
Dictyostelium promoters and introns is significantly higher than in the rest of
the genome. Fourteen selected sequences located in important genes were
characterized by a combination of biophysical and biochemical techniques.
Our data show that these sequences form highly stable G4 structures under
physiological conditions. Five Dictyostelium genes containing G4-prone motifs
in their promoters were studied for the effect of a new G4-binding porphyrin
derivative on their expression. Our results demonstrated that the new ligand
significantly decreased their expression. Overall, our results constitute the first
step to adopt Dictyostelium discoideum as a ‘G4-poor’ model for studies on
G-quadruplexes.
submitted by: Mona Saad [[log in to unmask]]
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