DNA repair pathway-related proteins are involved in the circularization step of microDNA eccDNAfib-L
Bibliographic record
Abstract
A large number of extrachromosomal circular DNAs (eccDNAs) are found in eukaryotic cells, but the mechanism behind the formation of eccDNAs remains unknown. EccDNAs smaller than 1000 bp are commonly referred to as microDNAs. In a prior study, we identified a 542 bp microDNA, designated eccDNAfib-L, mapping to Chromosome 14: 9,692,083-9,692,624 nt in the silk gland of Bombyx mori. There is a direct short repeat “GAGT” at both 5′ and 3′ break points of eccDNAfib-L, but only one copy of “GAGT” is retained in eccDNAfib-L. Here, we find that the specific junction observed can also be detected by transfecting with a DNA fragment containing upstream sequences of the 5′ break point and downstream sequences of the 3′ break point of eccDNAfib-L. Additionally, the length of the flanking sequences and the direct short repeats “GAGT” affect the formation efficiency of eccDNAfib-L. We confirm that eccDNAfib-L formation is associated with DNA repair pathways, with the expression of eccDNAfib-L undergoing significant alterations following the silencing of genes related to DNA repair pathways. In vitro, a cell-free reaction system confirms that Polθ and the direct short repeat “GAGT” are essential for the circularization of eccDNAfib-L, and the DExH-box helicase domain of Polθ plays critical role in mediating this circularization process. Collectively, our data support a mechanism whereby Polθ can mediate the joining of linear DNA fragments with direct short repeat at the 5′ and 3′ ends to form a circular DNA through MMEJ. The results not only clarify the essential factors driving eccDNAfib-L formation but also complement previous reports on eccDNA formation. DNA repair pathways are involved in eccDNAfib-L formation. Specifically, Polθ’s DExH-box helicase domain and direct short repeat “GAGT” are essential for its MMEJ-mediated circularization, delineating key factors driving this microDNA’s biogenesis.
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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 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".