DNA Damage Regulation of the RNA Components of the Translational Apparatus: New Biology and Mechanisms
Bibliographic record
Abstract
It was shown more than 30 years ago that expression of ribosomal (r) RNAs processed from the large precursor rRNA is repressed when eukaryotic cells are exposed to genotoxic stress. More recently it has been found that other RNA components of the translational machinery, the tRNAs and 5S rRNA transcribed by RNA polymerase (pol) III, are also downregulated in cells that have experienced DNA damage. In other words, the DNA damage response involves coordinate repression of genes whose products comprise the heart of the translational machinery. This repression could be due to blockage of polymerase elongation, and indeed this mechanism was originally invoked to explain repression of pol I-transcribed rRNAs under conditions of genotoxic stress. Recent work however reveals the existence of a DNA damage signaling pathway that directly contributes to downregulation of the pol III and probably the pol I transcription initiation machinery. This pathway involves a highly conserved protein kinase, CK2. Its likely target is the TATA Binding Protein, which in most eukaryotes is required for transcription by both pol I and pol III. Here I consider the implications of these findings for our understanding of the physiology of the DNA damage response, and for the prospect of developing a comprehensive molecular model of how cells cope with genotoxic stress.
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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) | 0.001 | 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".