Lysophosphatidylcholine Analogues Alter Yeast Nuclear Envelope Architecture and Function
Bibliographic record
Abstract
The lysophosphatidylcholine analog edelfosine is an anticancer lipid drug that targets cellular membranes. Therefore, it is alleged that in contrast to other chemotherapeutic agents edelfosine does not impact DNA. Despite this claim, a genetic screen in Saccharomyces cerevisiae found that lack of s ilent i nformation r egulator (Sir) proteins, alleviated the toxic effect of edelfosine. Since Sir proteins are key architects and regulators of the genome, we decided to investigate if this unusual connection with edelfosine could be related to a potential effect of the lysophosphatidylcholine analog on the nuclear envelope (NE) structure and function. Indeed, we found that edelfosine alters NE morphology, leading to an abnormal elongation of the membrane. Since it is known that Sir proteins mediate tethering of subtelomeric chromatin to the NE, we investigated if this was affected by treatment of wild type cells with the drug. Results from chromatin immunoprecipitation of Sir4 showed a significant reduction in the association of the protein with telomeres when cells were treated with edelfosine. Current evidence also supports alterations of telomere clustering in the presence of the lysophosphatidylcholine analogue. Therefore, our results suggest that edelfosine alters NE morphology and function. We speculate that mislocalization of Sir proteins in the nucleus probably results in abnormal silencing of genes that may be implicated in pathways that confer resistance to this lysophosphatidylcholine analog. Support or Funding Information This work has been financially supported by the Natural Sciences and Engineering Research Council of Canada to V Zaremberg and JA Cobb. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .
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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 | 0.000 | 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) | 0.000 | 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".