PARP enzyme synthesis of protein-free poly(ADP-ribose): Implications for DNA damage signaling and repair
Bibliographic record
Abstract
Poly(ADP-ribose) or PAR is a versatile signaling molecule with a broad impact on human biology. PAR is a prominent indicator of cellular DNA damage and genomic transactions such as replication and transcription. Canonically, human PARP enzymes create PAR as a modification on proteins. Recently, PARP enzymes were found to create free PAR molecules that are not attached to protein. Free PAR has been implicated in cell death signaling, but the production of free PAR was assumed to be generated by glycohydrolases breaking down protein-linked PAR into smaller fragments. The direct de novo production of free PAR by PARP1 occurs alongside the synthesis of protein-linked PAR in response to DNA damage, suggesting a more prevalent role for free PAR in DNA damage signaling. This review outlines the discovery of free PAR synthesis in biochemical reactions and in cellular models of the DNA damage response. The implications for this finding are summarized in the context of DNA damage signaling and associated processes of biomolecular condensate formation and Parthanatos cell death signaling.
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 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".