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Dsup, a protein unique to tardigrades, protects DNA from radiation: How does it do it?

The outstanding ability of tardigrades to survive environmental extremes has attracted an enormous attention in biology and biotechnology. Understanding the mechanisms of their exceptional resistance could be useful in many applications that range from the stabilization of pharmaceutical to the engineering of stress tolerant plants (see: https://www.uwyo.edu/molecbio/faculty-and-staff/thomas-boothby.html). The discovery that a protein named Dsup (damage suppressor), unique to tardigrades, protects DNA from damage produced by radiation and radicals raised expectations concerning its potential applications in biotechnology and medicine. While it was known that Dsup suppresses DNA damage induced by X-ray in human cultured cells and that it also binds to nucleosomes protecting chromosomal DNA from radical-mediated cleavage in vitro, no molecular explanation on this protecting role was available. From a structural point of view, the Dsup-DNA interaction posed a formidable challenge as the protein has no structure available and its sequence has no homologues.

Our study, which could be dubbed a “computational experiment in protein structure”, is the first description at atomic detail of the Dsup-DNA interaction and provides clues on how this singular protein protects DNA. Our results based upon computational modelling, molecular dynamics simulations, and calculations of electrostatic potentials and electric fields suggest that Dsup is a completely disordered protein from end to end. The abundance of positively charged amino acids drives Dsup's motion towards the negatively charged phosphates of DNA and its extreme flexibility allows Dsup adjust its structure to precisely fit DNA's shape. Our study reveals that effects associated to the electric field between Dsup and DNA provide a kind of electric shielding around DNA that might be crucial in protecting DNA from radiation.

Less than two weeks after publication of our article, it was covered by NewScientist that mentioned explicitly the CBGP (https://www.newscientist.com/article/2252583-secret-to-tardigrades-toughness-revealed-by-supercomputer-simulation/). Three weeks after publication, the paper reached an Altmetric 151, was in the 98th percentile, and had more than 3,100 accesses.

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Original Paper:

Mínguez-Toral, M., Cuevas-Zuviría, B., Garrido-Arandia, M., Pacios, L.F. 2020. A computational structural study on the DNA-protecting role of the tardigrade-unique Dsup protein. Scientific Reports 10, 13424. DOI: 10.1038/s41598-020-70431-1

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