Perinuclear chromosome tethers and RNA-DNA hybrid suppressors maintain genome stability and cellular lifespan
Bibliographic record
Abstract
Aging and related pathobiological conditions often involve genomic changes including alterations of repetitive DNA regions typically assembled into heterochromatin or silent chromatin structures. For example, telomeres and ribosomal DNA (rDNA) repeats are linked to aging in various organisms including yeast and humans. Our work has uncovered functions for the Cohibin protein complex in maintaining replicative lifespan of the budding yeast Saccharomyces cerevisiae through roles in tethering telomeres and rDNA repeats to the nuclear envelope. In addition, we found that the telomere-associated protein Rif1 sets the ideal lifespan-sustaining distribution of the conserved histone deacetylase Sir2 between telomeres and rDNA repeats. Moreover, we discovered distinct roles for the Cohibin-interacting protein Pbp1 in rDNA and lifespan maintenance via binding of intergenic non-coding RNA transcripts and subsequent suppression of RNA-DNA hybrids. We also uncover a role for the lifespan-promoting intervention known as caloric restriction in the engagement of magnesium-dependent hybrid suppressors to abolish hybrid accumulation associated with Pbp1 loss. In all, we discovered that perinuclear chromosome tethering and RNA-DNA hybrid suppression help maintain chromosome stability and cellular lifespan.
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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 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
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".