Polycomb group proteins in the DNA damage response: A link between radiation resistance and “stemness”
Bibliographic record
Abstract
Polycomb group proteins, which have well-established roles in gene regulation, were recently found to accumulate on chromatin surrounding DNA damage and to contribute up to 40 percent of the radiation resistance of cell lines. The oncogenic polycomb protein, BMI-1, was additionally shown to be essential for the increased radiation resistance observed in stem cells and cancer stem cells relative to their more differentiated counterparts. BMI-1, is a very early DNA damage response protein that accumulates through a γH2AX/RNF8-independent, but poly(ADP-ribosyl)ation-dependent mechanism at DNA double-strand breaks. BMI-1 acts together with RING2 and other components of the PRC1 histone H2A E3 ubiquitin ligase to ubiquitylate histones H2A and H2AX in response to DNA damage. BMI-1 dependent ubiquitin modifications are at the base of an ubiquitin pathway that enhances radioresistance through the accumulation of RAP80, 53BP1, and BRCA1. Members of the PRC2 histone H3 lysine 27 methyltransferase complex are also recruited to sites of DSBs but it remains to be determined whether the histone methyltransferase and histone E3 ubiquitin ligase polycomb complexes function in concert or independently during DNA repair. Understanding the contribution of polycomb group proteins to the DNA damage response may lead to novel therapeutic strategies that increase the response of human cancers to therapies that work through DNA damage, while simultaneously sensitizing the cancer stem cell population that would otherwise lead to relapse.
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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 | 0.000 | 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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 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".