Bibliographic record
Abstract
The error-free DNA lesion bypass pathway is a DNA damage tolerance response that switches replication templates with homologous recombination (HR) to fix DNA damage and ensure genomic authenticity. The spatial and temporal arrangement of proteins in the error-free lesion bypass pathway is largely undefined. The budding yeast Shu complex has been discovered to be crucial for DNA binding and other activities in the HR apparatus. The Shu complex structure has been determined and some key proteins of the error-free lesion bypass pathway have been identified. The molecular basis in which these proteins are organized remains unclear. We are working to characterize the structure and function of the Shu complex interacting with substrates through X-ray crystallography and related functional assays. The binding of specific DNA substrates would cause a conformational change to the Shu complex, which affects its ability to hydrolyze ATP. Structural data will help provide insights into the mechanism of the Shu complex and how it promotes the error-free bypass pathway at the molecular level. DNA substrates with different lengths and end natures were assayed via gel mobility shift and fluorescence polarization/anisotropy to identify substrates that interact best with the Shu complex. Preliminary data generated from malachite green ATPase assays suggest the Shu complex possess ATPase activity that is DNA-binding dependent. Thus far, crystals of the Csm2-Psy3 dimer in complex with DNA diffracted to a resolution of 2.8 in the space group of P312, which was different from the apo dimer's C2 space group. It is unclear if the DNA binding influenced the protein's structure without additional evidence from a structure with improved resolution. Additionally, crystals generated from Shu complex incubated with ATP and AMP-PNP diffracted in the same P43212 space group as the published Shu complex structure. Optimization of the crystallization condition for higher quality data is necessary to confirm the presence/absence of the substrates. In summary, structure built from the DNA-protein complex data could not confirm the DNA substrate relative to the Csm2-Psy3 dimer. Despite the ability to generate crystals, the substrate may not be the most suitable for the complex to consistently occupy a space in the structure. Optimization for better diffraction quality crystals of the Shu complex with ATP/AMP-PNP is underway. Conclusions drawn from this research will lay the foundation for understanding the mechanism of the error-free DNA damage tolerance to aid in combating various diseases like cancers and genetic defects.
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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 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 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".