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Link to original content: https://pubmed.ncbi.nlm.nih.gov/34681069
The Tardigrade Damage Suppressor Protein Modulates Transcription Factor and DNA Repair Genes in Human Cells Treated with Hydroxyl Radicals and UV-C - PubMed Skip to main page content
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. 2021 Sep 27;10(10):970.
doi: 10.3390/biology10100970.

The Tardigrade Damage Suppressor Protein Modulates Transcription Factor and DNA Repair Genes in Human Cells Treated with Hydroxyl Radicals and UV-C

Affiliations

The Tardigrade Damage Suppressor Protein Modulates Transcription Factor and DNA Repair Genes in Human Cells Treated with Hydroxyl Radicals and UV-C

Claudia Ricci et al. Biology (Basel). .

Abstract

The Ramazzottius varieornatus tardigrade is an extremotolerant terrestrial invertebrate with a length of 0.1-1.0 mm. These small animals show an extraordinary tolerance to extreme conditions such as high pressure, irradiation, chemicals and dehydration. These abilities are linked to a recently discovered damage suppressor protein (Dsup). Dsup is a nucleosome-binding protein that avoids DNA damage after X-ray and oxidative stress exposure without impairing cell life in Dsup-transfected animal and plant cells. The exact "protective" role of this protein is still under study. In human cells, we confirmed that Dsup confers resistance to UV-C and H2O2 exposure compared to untransfected cells. A different transcription factor activation was also observed. In addition, a different expression of endogenous genes involved in apoptosis, cell survival and DNA repair was found in Dsup+ cells after H2O2 and UV-C. In UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes, while H2O2 treatment only marginally involves the activation of pathways responsible for DNA repair in Dsup+ cells. These data are in agreement with the idea of a direct protective effect of the protein on DNA after oxidative stress. In conclusion, our data may help to outline the different mechanisms by which the Dsup protein works in response to different insults.

Keywords: DNA repair; Dsup; UV-C; oxidative stress; tardigrade; transcription factors.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Cell survival after 4 h (A) or O/N (B) treatment with increasing (250, 500, and 1000 µM) concentration of H2O2. Survival after 5″ (C) or 15″ (D) of UV-C exposure and 24 or 48 h of recovery. In all figures, 100% represents the basal condition (dotted line), gray bars are untransfected cells (indicated as control), and black bars are Dsup+ cells. * p < 0.5; ** p < 0.01; *** p < 0.001 by Wilcoxon signed-rank test. Each experiment was run in triplicate and was repeated at least three times. (E) Representative gel out of three of cyclobutane pyrimidine dimers (CPDs) formation in Dsup+ and untransfected cells (indicated as control) exposed to 5″ of UV-C and treated with T4 endonuclease V enzyme. Please refer to the Full agarose gel in the supplementary.
Figure 2
Figure 2
Transcription factor activation in Dsup+ and untransfected HEK293 (control) after 250 (panel (A)) or 1000 (panel (B)) µM H2O2 O/N or 5″ UV-C exposure (panel (C), 24 h of recovery and panel (D), 48 h of recovery). Results are reported as percentage over basal condition (100% and dotted lines in figure). MAPK pathway (ATF2, p-c-Jun, c-Myc, MEF2, STAT1α), AP-1 family (c-Fos, FosB, FRA-1, p-c-Jun, JunB, and JunD) and CREB/p-CREB expression were evaluated by ELISA. * p < 0.5; ** p < 0.01; *** p < 0.001 by Wilcoxon signed-rank test. Each point is the mean of triplicate wells.
Figure 3
Figure 3
Changes in transcription levels of selected endogenous genes in Dsup+ cells compared to untransfected cells exposed to H2O2 (µM) (A) and UV-C (B) expressed as heatmap. n.d.: Not detected. Each sample was run in triplicate and three biological replicates were performed.
Figure 4
Figure 4
STRING protein–protein interaction network for differentially expressed genes after H2O2 treatment (A) and UV-C exposure (B). Colored lines between the proteins indicate the various types of interaction evidence: a green line indicates neighborhood evidence; a purple line indicates experimental evidence; a light green line indicates text-mining evidence; a light blue line indicates database evidence; a black line indicates co-expression evidence.
Figure 5
Figure 5
Schematic model of protection mechanisms in mammalian cells expressing Dsup protein (Dsup+) exposed to oxidative stress and UV-C irradiation. After H2O2 treatment, Dsup+ cells mainly activate the detoxification system and antioxidant enzymes limiting oxidative stress, while DNA repair mechanisms are moderately turned on, probably due to DNA “physical” protection mediated by Dsup [8]. On the other hand, after UV-C exposure, Dsup+ cells respond by activating more efficient DNA repair genes reducing cyclobutane pyrimidine dimers formation. All these protective mechanisms give Dsup+ cells a greater resistance to external stress, improving their viability and growth respect to untransfected cells. ↑: moderate; ↑↑: high; ↓: low/reduced.

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