Evaluating Parp1 domains as gossypol targets
Bibliographic record
Abstract
Poly ADP-ribose Polymerase 1 (PARP1) is an important enzyme that is involved in DNA repair, replication, and transcription. Prospective anticancer drug gossypol inhibits human PARP1, but the mechanism of inhibition remains unknown. It has been shown previously that gossypol interacts with purified BRCA1 C-terminus (BRCT) domain in vitro. However, it remained unclear whether gossypol inhibits PARP1 through the BRCT domain in the context of full-length protein. Here, we report that the BRCT domain within the full-length PARP1 protein is not required for the inhibition of catalytic activity of PARP1 by gossypol. Our results, obtained using a series of PARP1 mutations and H4-dependent pathway of PARP1 activation, also show that none of the zinc fingers or other DNA binding domains of PARP1 are involved in the inhibition of the PARP1 catalytic activity by gossypol. Thus, the likely candidate target(s) for gossypol action are the other domains of PARP1, or the interdomain linkers.
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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 | 0.000 |
| 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 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.008 | 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; both teacher heads agree on what is shown here.
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".