Dsup

{{Short description|Tardigrade protein against DNA damage}}

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{{Infobox nonhuman protein

| Name = Damage suppressor protein

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| Organism = Ramazzottius varieornatus (tardigrade)

| TaxID = 947166

| Symbol = Dsup

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| UniProt = P0DOW4

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Dsup (contraction of damage suppressor) is a DNA-associating protein, unique to the tardigrade,{{cite news |last=Zimmer |first=Carl |title=What Makes Tiny Tardigrades Nearly Radiation Proof - New research finds that the microscopic "water bears" are remarkably good at repairing their DNA after a huge blast of radiation. |url=https://www.nytimes.com/2024/04/12/science/tardigrades-moss-piglets.html |date=12 April 2024 |work=The New York Times |url-status=live |archiveurl=https://archive.today/20240412184502/https://www.nytimes.com/2024/04/12/science/tardigrades-moss-piglets.html |archivedate=12 April 2024 |accessdate=13 April 2024 }} that suppresses the occurrence of DNA breaks by radiation.{{cite journal | vauthors = Hashimoto T, Kunieda T | title = DNA Protection Protein, a Novel Mechanism of Radiation Tolerance: Lessons from Tardigrades | journal = Life | volume = 7 | issue = 2 | pages = 26 | date = June 2017 | pmid = 28617314 | pmc = 5492148 | doi = 10.3390/life7020026 | doi-access = free | bibcode = 2017Life....7...26H }}{{cite journal | vauthors = Hashimoto T, Horikawa DD, Saito Y, Kuwahara H, Kozuka-Hata H, Shin-I T, Minakuchi Y, Ohishi K, Motoyama A, Aizu T, Enomoto A, Kondo K, Tanaka S, Hara Y, Koshikawa S, Sagara H, Miura T, Yokobori SI, Miyagawa K, Suzuki Y, Kubo T, Oyama M, Kohara Y, Fujiyama A, Arakawa K, Katayama T, Toyoda A, Kunieda T | title = Extremotolerant tardigrade genome and improved radiotolerance of human cultured cells by tardigrade-unique protein | journal = Nature Communications | volume = 7 | pages = 12808 | date = September 2016 | pmid = 27649274 | pmc = 5034306 | doi = 10.1038/ncomms12808 | bibcode = 2016NatCo...712808H }} 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,{{cite journal | vauthors = Horikawa DD, Sakashita T, Katagiri C, Watanabe M, Kikawada T, Nakahara Y, Hamada N, Wada S, Funayama T, Higashi S, Kobayashi Y, Okuda T, Kuwabara M | title = Radiation tolerance in the tardigrade Milnesium tardigradum | journal = International Journal of Radiation Biology | volume = 82 | issue = 12 | pages = 843–848 | date = December 2006 | pmid = 17178624 | doi = 10.1080/09553000600972956 | s2cid = 25354328 }} 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. However, subsequent research found that tardigrades, when hydrated, still remain highly resistant to shortwave UV radiation 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.{{cite web| vauthors = Horikawa DD |title=UV Radiation Tolerance of Tardigrades| url= https://astrobiology.nasa.gov/seminars/featured-seminar-channels/early-career-seminars/2012/04/24/uv-radiation-tolerance-of-tardigrades/ | archive-url= https://web.archive.org/web/20130218052059/https://astrobiology.nasa.gov/seminars/featured-seminar-channels/early-career-seminars/2012/04/24/uv-radiation-tolerance-of-tardigrades/ | url-status= dead | archive-date= 2013-02-18 |publisher= NASA.com |access-date= 2013-01-15}} A landmark study on Dsup protein showed that it can bind nucleosomes in the cell and protect DNA.{{cite journal | vauthors = Chavez C, Cruz-Becerra G, Fei J, Kassavetis GA, Kadonaga JT | title = The tardigrade damage suppressor protein binds to nucleosomes and protects DNA from hydroxyl radicals | journal = eLife | volume = 8 | pages = e47682 | date = October 2019 | pmid = 31571581 | pmc = 6773438 | doi = 10.7554/eLife.47682 | veditors = Jones KA, Tyler JK | doi-access = free }}

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.{{cite web |url=https://www.vice.com/en/article/scientists-identify-gene-that-protects-tardigrades-from-radiation/|title=Scientists Identify Gene That Protects Tardigrades From Radiation | vauthors=Turk V |date=20 September 2016 |work=Vice |access-date=19 May 2018}}

After hydrogen peroxide treatment Dsup+ cells mainly activate the detoxification systems and the antioxidant enzymes that limit oxidative stress and eliminate oxidative free radicals, while DNA repair mechanisms are only marginally activated.{{cite journal | vauthors = Ricci C, Riolo G, Marzocchi C, Brunetti J, Pini A, Cantara S | title = The Tardigrade Damage Suppressor Protein Modulates Transcription Factor and DNA Repair Genes in Human Cells Treated with Hydroxyl Radicals and UV-C | journal = Biology | volume = 10 | issue = 10 | page = 970 | date = September 2021 | pmid = 34681069 | pmc = 8533384 | doi = 10.3390/biology10100970 | doi-access = free }} Thus, upon induction of oxidative stress Dsup protein appears to mainly protect DNA directly.

Dsup protein has been found to be neurotoxic and promote neurodegeneration when expressed in cultured neurons by increasing DNA damage through the formation of double strand breaks.{{cite journal | vauthors = Escarcega RD, Patil AA, Meyer MD, Moruno-Manchon JF, Silvagnoli AD, McCullough LD, Tsvetkov AS | title = The Tardigrade damage suppressor protein Dsup promotes DNA damage in neurons | journal = Molecular and Cellular Neurosciences | volume = 125 | pages = 103826 | date = June 2023 | pmid = 36858083 | pmc = 10247392 | doi = 10.1016/j.mcn.2023.103826 }}