Dsup (contraction of ''damage suppressor'') is a

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

-associating

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

, unique to the

tardigrade Tardigrades (), known colloquially as water bears or moss piglets, are a phylum of eight-legged segmented micro-animals. They were first described by the German zoologist Johann August Ephraim Goeze in 1773, who called them . In 1776, th ...

, that suppresses the occurrence of DNA breaks by radiation. When human HEK293 cells were engineered with Dsup proteins, they showed approximately 40% more tolerance against X-ray radiation. Tardigrades can withstand 1,000 times more radiation than other animals, median lethal doses of 5,000 Gy (of gamma rays) and 6,200 Gy (of heavy ions) in hydrated animals (5 to 10 Gy could be fatal to a human). The only explanation found in earlier experiments for this ability was that their lowered water state provides fewer reactants for

ionizing radiation Ionizing (ionising) radiation, including Radioactive decay, nuclear radiation, consists of subatomic particles or electromagnetic waves that have enough energy per individual photon or particle to ionization, ionize atoms or molecules by detaching ...

. However, subsequent research found that tardigrades, when hydrated, still remain highly resistant to shortwave

UV radiation Ultraviolet radiation, also known as simply UV, is electromagnetic radiation of wavelengths of 10–400 nanometers, shorter than that of visible light, but longer than X-rays. UV radiation is present in sunlight and constitutes about 10% of t ...

in comparison to other animals, and that one factor for this is their ability to efficiently repair damage to their DNA resulting from that exposure. A landmark study on Dsup protein showed that it can bind nucleosomes in the cell and protect DNA. The Dsup protein has been tested on other animal cells. Using a culture of human cells that express the Dsup protein, it was found that after X-ray exposure the cells had fewer DNA breaks than control cells. After

hydrogen peroxide Hydrogen peroxide is a chemical compound with the formula . In its pure form, it is a very pale blue liquid that is slightly more viscosity, viscous than Properties of water, water. It is used as an oxidizer, bleaching agent, and antiseptic, usua ...

treatment Dsup+ cells mainly activate the

detoxification Detoxification or detoxication (detox for short) is the physiological or medicinal removal of toxic substances from a living organism, including the human body, which is mainly carried out by the liver. Additionally, it can refer to the period o ...

systems and the

antioxidant Antioxidants are Chemical compound, compounds that inhibit Redox, oxidation, a chemical reaction that can produce Radical (chemistry), free radicals. Autoxidation leads to degradation of organic compounds, including living matter. Antioxidants ...

enzymes that limit

oxidative stress Oxidative stress reflects an imbalance between the systemic manifestation of reactive oxygen species and a biological system's ability to readily detoxify the reactive intermediates or to repair the resulting damage. Disturbances in the normal ...

and eliminate oxidative free radicals, while

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

mechanisms are only marginally activated. Thus, upon induction of oxidative stress Dsup protein appears to mainly protect DNA directly. Dsup protein has been found to be

neurotoxic Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specifical ...

and promote neurodegeneration when expressed in cultured neurons by increasing DNA damage through the formation of double strand breaks.

Function and structure

The Dsup from ''

Ramazzottius ''Ramazzottius'' is a genus of water bear or moss piglet, a tardigrada, tardigrade in the class Eutardigrada, named after the Italian zoologist Giuseppe Ramazzotti. ''Ramazzottius varieornatus'' (see image) is a terrestrial invertebrate that is ...

varieornatus'' is mainly used for study, since it is one of the most stress-tolerant species. Orthologous versions of Dsup are also found in '' Hypsibius exemplaris'' (OQV24709, ). Dsup does not exhibit a lot of secondary structure, save for the helix in the middle. The C-terminal half contains an NLS, and this Ala/Gly-rich half is sufficient for DNA binding. It is probably mostly disordered, but it has a lot of positive charge. Dsup is known to bind to free DNA, but it binds more tightly to nucleosomes, the typical packed form of DNA in eukaryotic cells. Its nucleosome binding domain is vaguely similar to the one in HMGN proteins. Dsup localized to nuclear DNA reduces single-strand breaks and

double-strand breaks DNA repair is a collection of processes by which a cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is constantly modified ...

when subjected to

. Molecular dynamic simulation of Dsup in complex with DNA shows that it is an intrinsically disordered protein. Its flexibility and electrostatic charge helps it bind to DNA and form aggregates.

References

Animal proteins DNA-binding proteins Tardigrades {{Protein-stub