Characterization of the Mechanistic Roles of Rif1-Glc7 in DNA Double-Strand Break Repair Pathway Choice in Saccharomyces cerevisiae
Bibliographic record
Abstract
Rap-1 interacting factor 1 (Rif1) is a protein involved in telomere regulation, DNA replication and has more recently been found to mediate genomic stability by influencing the choice of DNA double-strand break (DSB) repair pathway. Rif1 and protein phosphatase 1 (PP1, Glc7 in budding yeast) prevent premature DNA replication initiation by maintaining dephosphorylation of the Mcm2-7 helicase, ensuring it remains inactive. Dbf4-dependent kinase (DDK) can counteract this at the onset of S phase by binding and phosphorylating Rif1 to prevent its interaction with PP1. It has recently been shown that Rif1 may similarly target PP1 to affect DSB repair pathway choice. However, the precise mechanisms involved remain unclear. \nTo examine the importance of the interaction between Rif1 and Glc7 in determining DNA DSB repair pathway choice, a rif1 5A∆PPDSPP mutant has been created by deleting the Dbf4 binding motif on Rif1 (PPDSPP), which allows DDK to phosphorylate Rif1, and by mutating 5 cyclin-dependent kinase (CDK) phosphorylation sites to alanine (5A), located \nnear the Glc7-binding site. Thus, this Rif1 mutant is not expected to be phosphorylated by DDK nor CDK, allowing Rif1-Glc7 to be constitutively active, resulting in an increase in Rif1-mediated Glc7 dephosphorylation activity. We find that this mutant is hypersensitive to DNA DSB-inducing agents and this sensitivity is partially rescued by abrogating the interaction between Rif1 and Glc7 through its conserved RVxF/SILK motifs. Partial rescue is additionally observed when Rif1 is unable to translocate to the inner nuclear membrane or bind to DNA ends at the DSB. Furthermore, upon DSB induction, less resection can be observed in this mutant strain, suggesting repair by the non-homologous end-joining (NHEJ) pathway. Through a series of experiments, this work demonstrates a role of Rif1 and Glc7, in the context of DNA DSBs, to promote repair by NHEJ.
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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 | 0.000 |
| 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".