Elevated mutagenesis and decreased DNA repair at a transgene are associated with proliferation but not apoptosis in p53-deficient cells
Bibliographic record
Abstract
p53, the most commonly mutated gene in human tumors, is believed to play a crucial role in the prevention of cancer by protecting cells from mutation, a theory commonly known as the "Guardian of the Genome" hypothesis. There are two hypotheses as to how this can occur. In the first, p53 protects the genome by retarding the cell cycle, thus allowing more time for DNA repair. In the second, p53 reduces cancer by initiating apoptosis in damaged cells, thus making it impossible for these cells to become carcinogenic. This study directly tested these two theories in primary murine embryonic fibroblasts on a common genetic background with and without p53, using a lacI transgene as a mutational target. The data demonstrate that, as a direct consequence of cell cycle delay, p53 slowed the induction of mutations and decreased their frequency but had little effect on the frequency of apoptosis. This indicates that the function of p53 in cell cycle control is more important than the role of p53 in apoptosis, for mutation prevention, in any uniform cell population. Moreover, p53-mediated protection is further improved in slowly dividing cells, suggesting that p53 may be particularly important in protecting stem cells from mutation. The role of apoptosis in vivo, however, may be to remove whole tissue subpopulations that can be renewed by less sensitive stem cells.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| 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".