Structural insights into γH2Ax containing nucleosomes
Bibliographic record
Abstract
The phosphorylation of the histone variant H2AX on the nucleosome, yielding γH2AX, acts as a 'master control switch', signaling the recruitment of DNA repair factors at DNA double-stranded break sites. This phosphorylation is recognized by BRCA1 carboxy-terminal (BRCT) domains of specific repair proteins. Using cryogenic electron microscopy (cryo-EM), we provide structural insights into diverse mononucleosome architectures and inter-nucleosomal interactions in the presence of H2AX, mimicking nucleosomes during DNA repair. We resolved three distinct stacked structures where the nucleosomal dyad axes and disk planes align parallel. The inter-nucleosomal interactions involve unique contacts mediated by the H4 N-terminal tail, exposed H2B elements, and DNA. Geometric analysis of stacking constraints, including published structures, reveals a tight distribution of rotational parameters around 0o, with the greatest variability in the translational parameter 'slide'. Our studies indicate that phosphorylation-dependent binding of BRCT domains with γH2AX nucleosomes disrupts stacking. However, no clear densities for BRCT proteins were observed, indicative of dynamic interactions. Molecular simulations replicate the stability of BRCT binding to γH2AX but do not indicate stable docked conformations of BRCT to nucleosome. We propose that BRCT recognition of γH2AX nucleosomes could contribute to chromatin decondensation during DNA damage signaling, exposing the nucleosomal acidic patch for repair factor recognition.
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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 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".