Assays of Bypass Replication of Genotoxic Lesions in Mammalian Disease and Mutant Cell-Free Extracts
Bibliographic record
Abstract
The genotoxic consequences of DNA damage in living organisms include short-term genetic instability and programmed cell death, as well as long-term inheritance of mutations and somatically acquired cancer. To respond to such constant genotoxic insults, living creatures from viruses to humans have evolved the capacity to remove or tolerate DNA lesions. Although the first process is generally referred to as DNA repair, the latter one has been described in the eukaryotic literature as postreplication repair, translesion synthesis, or bypass replication. Numerous lines of evidence suggest that replication of DNA lesions is often an essential triggering factor in the induction of deleterious genetic effects ( 1 ). First, proliferating cells are more susceptible to neoplastic transformation than nonproliferating cells after genotoxic treatment. Second, mutation rates increase dramatically during S-phase of cells pre-exposed to DNA-damaging agents. Third, DNA damage stimulates replication-dependent clastogenic phenomena in mammalian cells, such as sister-chromatid exchanges, chromosomal aberrations, and gene amplification. Fourth, several cancer-prone syndromes present constitutional abnormalities in the recovery of replication after DNA damage ( see Chapter 44 ). Because of such clear evidence for the primary role played by replication of DNA lesions on processes leading to genetic instability, it is important to understand the mechanisms of lesion persistence in eukaryotic cells. These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".