DnaA, ORC, and Cdc6: similarity beyond the domains of life and diversityThis paper is one of a selection of papers published in this special issue entitled 8th International Conference on AAA Proteins and has undergone the Journal's usual peer review process.
Bibliographic record
Abstract
To initiate chromosomal DNA replication, specific proteins bind to the replication origin region and form multimeric and dynamic complexes. Bacterial DnaA, the eukaryotic origin recognition complex (ORC), and Cdc6 proteins, most of which include an AAA+(-like) motif, play crucial roles in replication initiation. The importance of ATP binding and hydrolysis in these proteins has recently become recognized. ATP binding of Escherichia coli DnaA is required for the formation of the activated form of a DnaA multimer on the replication origin. The ATP-DnaA multimer can unwind duplex DNA in an origin-dependent manner, which is supported by various specific functions of several AAA+ motifs. DnaA-ATP hydrolysis is stimulated after initiation, repressing extra initiations, and sustaining once-per-cell cycle replication. ATP binding of ORC and Cdc6 in Saccharomyces cerevisiae is required for heteromultimeric complex formation and specific DNA binding. ATP hydrolysis of these proteins is important for the efficient loading of the minichromosome maintenance protein complex, a component of the putative replicative helicase. In this review, we discuss the roles of DnaA, ORC, and Cdc6 in replication initiation and its regulation. We also summarize the functional features of the AAA+ domains of these proteins, and the functional divergence of ORC in chromosomal dynamics.
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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) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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".