Dynamic chromatin modifications during repair of DNA double strand breaks
Bibliographic record
Abstract
The NuA4 histone acetyltransferase is a highly conserved multisubunit complex responsible for acetylation of nucleosomal histone H4 and H2A. Mutations in different NuA4 subunits create cell cycle arrest or delay in G2/M. The NuA4 complex is important for the efficient repair of DNA double strand breaks (DSBs) in vivo. NuA4 is rapidly recruited on chromatin surrounding a DSB in vivo at the same time histone H2A is phosphorylated at serine 129 in the neighboring region. This modification is functionally equivalent to the phosphorylation of H2AX Ser139 in mammals. ATP‐dependent chromatin remodeling complex Ino80 and the Rvb1 helicase are also recruited upon formation of a DSB in vivo but are delayed compared to NuA4. Prior chromatin acetylation by NuA4 is required for efficient Ino80/Rvb1 binding. Furthermore, NuA4 dependent acetylation of chromatin around a DSB is lost 2–4 hrs after break formation, at the same time we detect local phosphorylation of histone H4 at serine 1 by CKII. This mark blocks reacetylation by the NuA4 complex and could be linked to restoration of chromatin after repair/adaptation. In addition, we found that NuA4 is phosphorylated in response to DNA damage and its recruitment to the DSB is regulated during the cell cycle. Finally, NuA4 role in DNA repair is functionally linked to Rad9 signaling and Dot1‐dependent methylation of histone H3. Local regulation of NuA4 activity/retention by specific sequential histone phosphorylation events and stepwise action of chromatin modifiers/remodelers are certainly important mechanisms used by the cell to allow efficient DNA repair and the maintenance of genome integrity. This work is supported by a grant from the Canadian Institutes of Health Research.
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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 | 0.001 |
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".