Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination
Bibliographic record
Abstract
Significance DNA lesions initiated by activation-induced cytidine deaminase (AID) during class switch recombination (CSR) are diverse, and knowledge of the relationship between specific DNA lesions and DNA repair outcomes remains incomplete. Using the Cas9 endonuclease, we show that Cas9 models AID-mediated lesions leading to CSR and chromosomal translocations, and that double-stranded DNA breaks (DSBs) with 5′ overhangs skew intrachromosomal and interchromosomal end-joining toward alternative end-joining. These data establish a role for DSB end polarity in choosing the DNA repair pathway. This work provides a greater understanding of how diverse DNA lesions are differentially repaired, which will improve our understanding of the mechanism of physiological processes required for adaptive immunity and protective mechanisms that maintain genomic integrity from diverse threats.
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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".