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Multivalent binding of the tardigrade Dsup protein to heterologous chromatin promotes yeast survival and longevity upon exposure to oxidative damage

ABSTRACT: Multivalent binding of the tardigrade Dsup protein to heterologous chromatin promotes yeast survival and longevity upon exposure to oxidative damage

PROVIDER: PRJNA994949 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR25281500_1.fastq.gz	Fastqsanger.gz
	SRR25281500_2.fastq.gz	Fastqsanger.gz
	SRR25281501_1.fastq.gz	Fastqsanger.gz
	SRR25281501_2.fastq.gz	Fastqsanger.gz
	SRR25281502_1.fastq.gz	Fastqsanger.gz

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Multivalent binding of the tardigrade Dsup protein to heterologous chromatin promotes yeast survival and longevity upon exposure to oxidative damage

Project description:Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends the lifespan of budding yeast with chronic oxidative damage. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.

2024-01-14 | GSE237436 | GEO

Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage

Project description:Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage

| PRJNA1247871 | ENA

Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage

Project description:Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought to contribute to their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends lifespan in response to chronic oxidative genotoxicity. Dsup uses multiple modes of engagement with the nucleosomal H2A/H2B acidic patch, H3/H4 histone tails and DNA to bind across the yeast genome without bias. Effective chromatin binding and genome protection requires the Dsup HMGN-like motif and C-terminal sequences. These findings give precedent and mechanistic understanding for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.

2025-04-08 | GSE294019 | GEO

Multivalent binding of the tardigrade Dsup protein to chromatin promotes yeast survival and longevity upon exposure to oxidative damage.

Project description:Tardigrades are remarkable in their ability to survive extreme environments. The damage suppressor (Dsup) protein is thought responsible for their extreme resistance to reactive oxygen species (ROS) generated by irradiation. Here we show that expression of Ramazzottius varieornatus Dsup in Saccharomyces cerevisiae reduces oxidative DNA damage and extends the lifespan of budding yeast exposed to chronic oxidative genotoxicity. This protection from ROS requires either the Dsup HMGN-like domain or sequences C-terminal to same. Dsup associates with no apparent bias across the yeast genome, using multiple modes of nucleosome binding; the HMGN-like region interacts with both the H2A/H2B acidic patch and H3/H4 histone tails, while the C-terminal region binds DNA. These findings give precedent for engineering an organism by physically shielding its genome to promote survival and longevity in the face of oxidative damage.

| S-EPMC10402244 | biostudies-literature

The tardigrade Hypsibius exemplaris dramatically upregulates DNA repair pathway genes in response to ionizing radiation [IR_RNA-seq]

Project description:Tardigrades can survive remarkable doses of ionizing radiation, up to about 1000 times the lethal dose for humans. How they do so is incompletely understood. We found that the tardigrade Hypsibius exemplaris suffers DNA damage upon gamma irradiation, but damage is repaired. We show that this tardigrade has a specific and robust response to ionizing radiation: irradiation induces a rapid upregulation of many DNA repair genes. This upregulation is unexpectedly extreme, making some DNA repair transcripts among the most abundant transcripts in the animal. By expressing tardigrade genes in bacteria, we validate that increased expression of some repair genes can suffice to increase radiation tolerance. We show that at least one such gene is important for tardigrade radiation tolerance. We hypothesize that tardigrades’ ability to sense ionizing radiation and massively upregulate specific DNA repair pathway genes may represent an evolved solution for maintaining DNA integrity.

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Transcriptome analysis of the extremophile tardigrade Hypsibius exemplaris exposed to the DNA-damaging agent bleomycin

Project description:Transcriptome analysis of the extremophile tardigrade Hypsibius exemplaris exposed to the DNA-damaging agent bleomycin

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The tardigrade Hypsibius exemplaris dramatically upregulates DNA repair pathway genes in response to ionizing radiation [Bleo_RNA-seq]

Project description:Tardigrades can survive remarkable doses of ionizing radiation, up to about 1000 times the lethal dose for humans. How they do so is incompletely understood. We found that the tardigrade Hypsibius exemplaris suffers DNA damage upon gamma irradiation, but damage is repaired. We show that tardigrades have a specific and robust response to ionizing radiation: irradiation induces a rapid and dramatic upregulation of many DNA repair genes. By expressing tardigrade genes in bacteria, we validate that increased expression of some repair genes can suffice to increase radiation tolerance. We show that at least one such gene is necessary for tardigrade radiation tolerance. Tardigrades’ ability to sense ionizing radiation and massively upregulate specific DNA repair pathway genes may represent an evolved solution for maintaining DNA integrity.

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Project description:Tardigrades are microscopic invertebrates renowned for their ability to survive extreme environmental stress such as radiation, extreme temperatures, and desiccation. Yet, the biochemical mechanisms they utilize to survive these extremes are poorly understood. Herein, we implement proteomics to investigate the biomolecular underpinnings of tardigrade osmobiosis – a survival state in response to osmotic pressure. Using two solutes, the non-ionic sucrose and the ionic NaCl, we reveal that de novo gene expression is not required for osmobiosis induction. While sucrose and NaCl induce slightly different proteomic effects, both solutes lead to an increased abundance or oxidation of proteins involved in ER or mitochondrial activity. Further, we investigate the role of mitochondria in tardigrade osmobiosis and demonstrate that inhibition of the alternative oxidase (AOX) within the mitochondrial respiratory chain (MRC) increases the rate of osmobiosis formation across both sucrose and NaCl. Subsequent electron paramagnetic resonance (EPR) spectroscopy reveals an increased rate of reactive oxygen species (ROS) formation in osmobiotes with AOX inhibited, suggesting a regulation of osmobiosis through MRC-derived ROS. In sum, this work suggests mitochondrial-ROS signaling is necessary for tardigrade osmobiosis and further clarifies the biochemical mechanisms contributing to tardigrade extremotolerance.

2025-07-14 | PXD058865 | Pride

Multivalent Influenza DNA vaccine induces cross-reactive polyfunctional T lymphocytes and promotes rapid clearance of heterologous challenge strain in non-human primates

Project description:Recent avian and swine-origin influenza virus outbreaks illustrate the ongoing threat of influenza pandemic. New vaccines that offer accelerated production and broader, more universal protection against drifted and shifted strains are needed. Here, we investigated a multivalent PMED DNA vaccine for the ability to induce antibody and T cell responses against four HA antigens, nucleoprotein and the ectodomain of M2 (M2e). Macaques in the Vaccinated and Control groups were intramuscularly anaesthetized with ketamine (10 mg/kg) and inoculated with a suspension containing 10^6.5 p.f.u. ml-1 of CA09 virus through a combination of intratracheal (4.5 ml), intranasal (0.5 ml per nostril), ocular (0.1 ml per eye) and oral (1 ml) routes (resulting in a total infectious dose of 10^7.4 PFU). Bronchoalveolar lavages were collected two weeks prior to challenge and at days 3, 7, and 10 post-infection. We performed microarray analysis on these samples.

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Multivalent Influenza DNA vaccine induces cross-reactive polyfunctional T lymphocytes and promotes rapid clearance of heterologous challenge strain in non-human primates

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