Bibliographic record
Abstract
2624 DNA palindromes consist of pairs of inversely repeated sequences having central symmetry that, along with forming typical B-form double helices, are able to form intra-strand hairpin and cruciform structures. However, the ability of palindromes to form hairpins and cruciforms poses a special threat to the genome as these secondary structures can block replication and lead to genetic rearrangements. In human and rodent systems, a unique mechanism for dealing with palindromes has been demonstrated, termed the Center-Break Model. In this mechanism, each of the hairpin tips are nicked, creating a double strand break at the center of symmetry. This break is then repaired by the NHEJ pathway, a process which often results in deletion of sequence creating a central asymmetry. While sequence analysis of breakpoints demonstrates the Center-Break mechanism, it is unknown which pathway(s) of detection and repair functions are involved. Investigations are being undertaken using both chromosomally and extra-chromosomally located palindromes combined with genetic knock-out and knock-down techniques in order to implicate both proteins and a potential pathway. For the chromosomal palindrome investigation, a mouse model carrying a 15.6kb perfect palindrome on chromosome 17, termed the Line 78 mouse is being used. The role of several proteins in palindrome processing are being tested, the first being the Werner’s syndrome protein because it is required for genome stability and affects the stability of the Tg.AC palindrome. Also, the potential roles for DNA-Pk, Ku70 because of their roles in NHEJ, and Artemis, as the hairpin-nicking nuclease in V(D)J recombination are being explored. Abelson cell lines generated from crosses of these mice are then monitored for palindrome rearrangement using subcloning, inverse-PCR and Southern blot techniques. Previous work in the lab had shown that the rate of rearrangement of the Line 78 palindrome in different wild-type backgrounds is 0.5% per generation. By determining the rate of rearrangement, as well as the quality (i.e. larger versus small deletions), in a variety of genetic backgrounds, I will be able to implicate various proteins and pathways in the process of palindrome rearrangement. The second approach to investigate the role of DNA repair functions in palindrome instability is an extra-chromosomal transfection assay. This approach examines rearrangement of a palindromic circular dimer, which can be transfected into cell cultures of interest. This palindrome is reproducibly and site-specifically resolved into monomer circles. This assay is being carried out in cell lines of the genetic backgrounds mentioned above, and is also being combined with RNAi techniques in oreder to expand the number of genetic influences that can be examined. This extra-chromosomal transfections assay will allow for rapid and varied investigation of the role of certain proteins in palindrome processing.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".