Human telomerase determinants of processivity and fidelity
Bibliographic record
Abstract
Telomeres are dynamic nucleoprotein complexes that protect the fragile termini of chromosomes. Without telomeres, chromosome ends are recognized as DNA breaks and inclined to nucleolytic degradation and end-to-end fusions. Telomeres consist of DNA repeats that are synthesized by telomerase, a specialized reverse transcriptase (RT) enzyme minimally composed of a catalytic protein subunit (TERT) and an essential RNA component (TR). Although the functional aspects of telomerase are not well elucidated, this ribonucleoprotein enzyme clearly regulates cellular life-span through its ability to maintain or elongate telomeres. Human TERT (hTERT) has a central region containing conserved (RT)-like motifs, and N- and C-terminal regions that are unique to the TERT family. We analysed the precise role of the C-terminus of hTERT by introducing small deletions and amino acid substitutions throughout the C-terminal region, and demonstrated that the hTERT C-terminal region is essential for enzyme catalysis in vitro. We reported that hTERT multimerization requires the presence of catalytically essential C-terminal amino acid residues and intact RT-like motifs on the same hTERT molecule. We also examined DNA synthesis at nucleotide resolution with a direct primer extension assay, and found that the hTERT C-terminus modulates telomerase processivity. In addition, we reported that human telomerase reconstituted in rabbit reticulocyte lysate (RRL) and partially purified telomerase from human cells catalyze the cleavage of DNA substrates prior to their elongation. Finally, we determined the experimental conditions for human telomerase expression in insect cells in order to obtain an abundant source of catalytically active recombinant telomerase.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.012 | 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".