Dual DNA-binding capability of Cdc13 coordinates with Ku to safeguard telomere integrity
Bibliographic record
Abstract
Abstract In eukaryotes, telomeres, nucleoprotein complexes assembled on telomeric 3’-overhang DNA, protect linear chromosome ends from degradation and inappropriate DNA repair. In budding yeast, Saccharomyces cerevisiae, telomere assembly involves the Cdc13-Stn1-Ten1 (CST) complex, the Ku70-Ku80 (Ku) complex, and the Rap1-Rif1-Rif2 complex. Among these, the CST complex, centered on the binding of the G-rich single-stranded region by the Cdc13 subunit, is essential for telomere maintenance and protection. Here, we show that Cdc13 also interacts with the duplex DNA adjoining its bound single strand. This junction binding enables Cdc13 to reposition the Ku complex, potentially suppressing Ku-mediated end joining, while allowing the Cdc13 and Ku complexes to synergize in protecting telomeric DNA ends, a function that can be disrupted by mutation of a conserved residue (K504E). cdc13-K504E cells remain viable but are hypersensitive to Exo1 overexpression, particularly when combined with ku80Δ . Surprisingly, cdc13-K504E and other telomere protection mutants are prone to adaptive metabolic reprogramming during stationary-phase growth, leading to increased fitness. This reprogramming is inheritable and centers on elevated expression of thiamine biosynthesis, salvage, and intake pathways. Our findings reveal a stress-induced adaptive response associated with telomere erosion, indicating that telomere erosion may serve as a timer for its activation.
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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) | 0.002 | 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".