Conversion of a telomere resolvase into a Cre-like site-specific recombinase
Bibliographic record
Abstract
Hairpin telomere resolvases are a unique family of enzymes involved in producing the hairpin (hp) telomeres of bacterial organisms and phages that possess linear DNA's terminated by hp telomeres. The hp telomeres help to overcome the end-replication problem faced by linear DNAs and are generated from replicated intermediates of the linear DNAs. The telomere resolvases employ a reaction mechanism and catalytic domain related to that of the type IB topoisomerases and tyrosine recombinases. ResT, the telomere resolvase from Borrelia burgdorferi, under certain reaction conditions, has been shown to promote site-specific recombination between replicated telomere junctions (rTels) to produce a Holliday junction intermediate in a reaction strikingly similar to that promoted by tyrosine recombinases. TelA, the telomere resolvase of Agrobacterium tumefaciens, has been shown to be autoinhibited in such a manner as to forbid recombination between rTels. Relief of such autoinhibition reveals a weak, cryptic recombination activity in TelA. In the present study we characterize a catalytic domain aspartic acid residue mutation (D398A) that produces an enzyme with compromised telomere resolution activity but a massively stimulated ability to promote recombination between replicated telomere junctions to produce both the Holliday junction intermediate and full recombinant products of site-specific recombination between rTels. We also report that combination of the D398A mutation with previously characterized hyperactivating mutations in TelA produced a complete conversion of a telomere resolvase into a site-specific recombinase. The possible utility of this conversion is explored.
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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 | 0.001 | 0.000 |
| Research integrity | 0.001 | 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".