Constitutive methylation of budding yeast CENP-A contributes to chromosomal instability
Bibliographic record
Abstract
Centromere (CEN) identity is specified epigenetically by specialized nucleosomes \ncontaining evolutionarily conserved CEN-specific histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae, CENP-A in humans), which is essential for faithful chromosome segregation. However, the epigenetic mechanisms that regulate Cse4 function have not been fully \ndefined. In this study, we show that cell cycle-dependent methylation of Cse4-R37 regulates \nkinetochore function and high-fidelity chromosome segregation. We generated a custom \nantibody that specifically recognizes methylated Cse4-R37 and showed that methylation of \nCse4 is cell cycle regulated with maximum levels of methylated Cse4-R37 and its enrichment \nat the CEN chromatin occur in the mitotic cells. Methyl-mimic cse4-R37F mutant exhibits \nsynthetic lethality with kinetochore mutants, reduced levels of CEN-associated kinetochore \nproteins and chromosome instability (CIN), suggesting that mimicking the methylation of \nCse4-R37 throughout the cell cycle is detrimental to faithful chromosome segregation. Our \nresults showed that SPOUT methyltransferase Upa1 contributes to methylation of Cse4-R37 \nand overexpression of UPA1 leads to CIN phenotype. In summary, our studies have defined \na role for cell cycle-regulated methylation of Cse4 in high-fidelity chromosome segregation \nand highlight an important role of epigenetic modifications such as methylation of kinetochore proteins in preventing CIN, an important hallmark of human cancers.
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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".