Estrogen receptor α-mediated transcription induces cell cycle-dependent DNA double-strand breaks
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
Prolonged exposure to estrogen increases breast cancer risk. Estrogen is known to induce chromosomal aberrations, yet the mechanisms by which estrogen promotes genomic instability are not fully understood. Here, we show that exposure of MCF-7 cells to 17β-estradiol (E2) induces DNA double-strand breaks (DSBs), as determined by the formation of γH2AX foci. Foci formation was dependent upon estrogen receptor-α (ERα) and the catalytic activity of the type II topoisomerase, topoisomerase IIβ (topoIIβ). Moreover, we show by chromatin immunoprecipitation that topoIIβ-dependent E2-induced γH2AX localizes to the promoter of the estrogen-inducible gene, trefoil factor 1. E2-induced foci were associated with cyclin A expression and inhibited by pre-incubation with the DNA polymerase inhibitor aphidicolin suggesting that E2-induced DSBs are mediated by progression through S phase. Furthermore, E2-induced γH2AX foci colocalized with Rad51, suggesting that E2-induced DSBs are repaired by homologous recombination. We propose that DNA DSBs formed by the strand-cleaving activity of the topoIIβ-DNA cleavage complex at estrogen-inducible genes can present a barrier to DNA replication, leading to persistent DNA DSBs in ERα-positive breast cancer cells.
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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 it