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 distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 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 teacher head, 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".