Structural and Functional Studies of Non-Homologous End-Joining Regulator 1 (NEJ1)
Bibliographic record
Abstract
Repair of double-strand breaks is critical for the preservation of genomic integrity and cellular viability. A predominant pathway implicated in the repair of such lesions is the evolutionarily conserved non-homologous end-joining (NHEJ) pathway. Among the major constituents of this pathway in Saccharomyces cerevisiae is Nej1, for which a clear biochemical function has not been determined. The results presented in this work demonstrate that Nej1 exhibits a DNA binding activity comparable to Lif1, with an apparent dissociation constant of 1.8 μM. Characterization of the DNA binding activity revealed that although short ~20 bp substrates can suffice, binding is enhanced with longer substrates (>300). This DNA binding activity supports the hypothesis that Nej1 plays a direct role in the repair of DNA double-strand breaks. Structure-function studies indicated that the C-terminus of Nej1 is not only required, but is sufficient, for mediating DNA interactions. Structural characterization revealed that Nej1 exists as a dimer, and that residues 1-244 are sufficient for dimer formation. Examining the ability of this truncated Nej1 (aa 1-244) to perform NHEJ, revealed a defect in end-joining as measured by an in vivo plasmid repair assay. Preliminary functional and structural studies on the Nej1-Lif1 complex suggest that the proteins stably co-purify and the complex binds DNA with a higher affinity than each independent component. The significance of these results is discussed with reference to current literature on Nej1 and other end-joining factors (mammalian and yeast), specifically the recently identified putative mammalian homologue of Nej1, XLF. Collectively, these results demonstrate that although there are several functional similarities, there also appear to be important differences in the structure-function relationships of Nej1 and XLF, and Nej1/XLF and Lif1/Xrcc4.
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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 | 0.000 |
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 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".