DNA Polymerase θ Increases Mutational Rates in Mitochondrial DNA
Bibliographic record
Abstract
Replication and maintenance of mitochondrial DNA (mtDNA) is essential for cellular function, yet few DNA polymerases are known to function in mitochondria. Here, we conclusively demonstrate that DNA polymerase θ (Polθ) localizes to mitochondria and explore whether this protein is overexpressed in patient-derived cells and tumors. Polθ appears to play an important role in facilitating mtDNA replication under conditions of oxidative stress, and this error-prone polymerase was found to introduce mutations into mtDNA. In patient-derived cells bearing a pathogenic mtDNA mutation, Polθ expression levels were increased, indicating that the oxidative conditions in these cells promote higher expression levels for Polθ. Heightened Polθ expression levels were also associated with elevated mtDNA mutation rates in a selected panel of human tumor tissues, suggesting that this protein can influence mutational frequencies in tumors. The results reported indicate that the mitochondrial function of Polθ may have relevance to human disease.
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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 | 0.001 |
| 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".