Friend and Foe: Genome-Wide Analysis of the Tardigrade Dsup Protein Expressed in Yeast Reveals Trade-offs of DNA Protection
Bibliographic record
Abstract
Abstract Tardigrades are among the most resilient eukaryotes known, capable of surviving a wide range of extreme conditions. While their genomes contain thousands of tardigrade-specific genes, one key contributor to their stress resistance is the Damage suppressor (Dsup) protein. Previous work showed that expression of Dsup in cancer cells reduced DNA damage caused by X-rays. This observation has sparked growing interest in Dsup across diverse model organisms. Most studies to date have focused on phenotypic outcomes, while the mechanisms and consequences of Dsup remain poorly understood. Deciphering its mechanism is crucial, especially because Dsup expression is deleterious to some cells and organisms. In this work, we show that Dsup protects yeast against a variety of DNA-damaging agents. However, this protection is not universal, and it has a fitness cost. Analysis of nucleosome occupancy of cells expressing Dsup shows that effects on chromatin are modest, without global remodeling, and transcriptome analysis reveals a robust induction of oxidative stress pathways, which might be a form of preconditioning for oxidative stress. Genome-wide screens of ∼4300 loss-of-function mutants expressing Dsup shows that deletions incompatible with Dsup are highly enriched for DNA repair processes and that under DNA damage stress, Dsup can protect some mutants in a pathway-specific manner. Our findings demonstrate that while Dsup broadly enhances resistance to genotoxic stress, it also imposes physiological costs and generates new dependencies on DNA repair and genome maintenance pathways.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".