p53-dependent DNA repair during the DNA damage response requires actin nucleation by JMY
Bibliographic record
Abstract
The tumour suppressor p53 is a nuclear transcription factor with key roles during DNA damage to enable a variety of cellular responses including cell cycle arrest, apoptosis and DNA repair. JMY is an actin nucleator and DNA damage-responsive protein whose sub-cellular localisation is responsive to stress and during DNA damage JMY undergoes nuclear accumulation. To gain an understanding of the wider role for nuclear JMY in transcriptional regulation, we performed transcriptomics to identify JMY-mediated changes in gene expression during the DNA damage response. We show that JMY is required for effective regulation of key p53 target genes involved in DNA repair, including XPC, XRCC5 (Ku80) and TP53I3 (PIG3). Moreover, JMY depletion or knockout leads to increased DNA damage and nuclear JMY requires its Arp2/3-dependent actin nucleation function to promote the clearance of DNA lesions. In human patient samples a lack of JMY is associated with increased tumour mutation count and in cells results in reduced cell survival and increased sensitivity to DNA damage response kinase inhibition. Collectively, we demonstrate that JMY enables p53-dependent DNA repair under genotoxic stress and suggest a role for actin in JMY nuclear activity during the DNA damage response.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".