The histone chaperone FACT coordinates H2A.X-dependent signaling and repair of DNA damage
Bibliographic record
Abstract
SUMMARY Safeguarding cell function and identity following a genotoxic stress challenge entails a tight coordination of DNA damage signaling and repair with chromatin maintenance. How this coordination is achieved and with what impact on chromatin integrity remains elusive. Here, by investigating the mechanisms governing the distribution of H2A.X in mammalian chromatin, we demonstrate that this histone variant is deposited de novo at sites of DNA damage in a repair synthesis-coupled manner. Our mechanistic studies further identify the histone chaperone FACT (Facilitates Chromatin Transcription) as responsible for the deposition of newly synthesized H2A.X. Functionally, FACT potentiates H2A.X-dependent signaling of DNA damage and, together with ANP32E (Acidic Nuclear Phosphoprotein 32 Family Member E), orchestrates a H2A.Z/H2A.X exchange reaction that reshapes the chromatin landscape at repair sites. We propose that this mechanism promotes chromatin accessibility and helps tailoring DNA damage signaling to repair progression. HIGHLIGHTS H2A.X, but not H2A.Z, is deposited de novo at sites of DNA damage repair FACT promotes new H2A.X deposition coupled to repair synthesis FACT and ANP32E chaperones orchestrate H2A.Z/H2A.X exchange in damaged chromatin FACT stimulates H2A.X-dependent signaling of DNA damage
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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 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".