Specific basic patch‐dependent multimerization of <i>Saccharomyces cerevisiae</i> ORC on single‐stranded DNA promotes ATP hydrolysis
Bibliographic record
Abstract
Replication initiation at specific genomic loci dictates precise duplication and inheritance of genetic information. In eukaryotic cells, ATP-bound origin recognition complexes (ORCs) stably bind to double-stranded (ds) DNA origins to recruit the replicative helicase onto the origin DNA. To achieve these processes, an essential region of the origin DNA must be recognized by the eukaryotic origin sensor (EOS) basic patch within the disordered domain of the largest ORC subunit, Orc1. Although ORC also binds single-stranded (ss) DNA in an EOS-independent manner, it is unknown whether EOS regulates ORC on ssDNA. We found that, in budding yeast, ORC multimerizes on ssDNA in vitro independently of adenine nucleotides. We also found that the ORC multimers form in an EOS-dependent manner and stimulate the ORC ATPase activity. An analysis of genomics data supported the idea that ORC-ssDNA binding occurs in vivo at specific genomic loci outside of replication origins. These results suggest that EOS function is differentiated by ORC-bound ssDNA, which promotes ORC self-assembly and ATP hydrolysis. These mechanisms could modulate ORC activity at specific genomic loci and could be conserved among eukaryotes.
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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 | 0.000 |
| 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) | 0.000 | 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".