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

水熊虫损伤抑制蛋白能够调节经羟基自由基和UV-C处理的人类细胞中的转录因子和DNA修复基因。

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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 H(2)O(2) 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 H(2)O(2) and UV-C. In UV-C exposed cells, Dsup efficiently upregulates DNA damage repair genes, while H(2)O(2) 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.

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