The Silencing Face of DNA Replication: Gene Repression Mediated by DNA Replication Factors
Bibliographic record
Abstract
IntroductionDNA replication in eukaryotes initiates at multiple origins.The activation of these origins is a critically important event in the life of each cell and is tightly regulated by numerous highly conserved trans-factors.Saccharomyces cerevisiae origins (called Autonomously Replicating Sequences, ARSs) contain a core A element called ACS (ARS Consensus Sequence), plus an array of auxiliary B elements.Most ARSs fire at their chromosomal positions, but there are numerous dormant ARSs as well.Instead of being origins, these dormant ARSs serve as silencer elements, which function in the epigenetic repression of nearby genes.Even more, many DNA replication trans-factors have also been reported to affect gene silencing.This puzzling functional duality of ARS and DNA replication factors has attracted significant interest.Evidence from other species has suggested that the overlap between gene silencing and DNA replication operates in other eukaryotes.In this chapter we will review in detail the activity of ARSs as origins of replication and as silencers.We will focus on sequence dissimilarities between silencer and origin ARSs and will propose a model for the functional duality of DNA replication factors. Origins of DNA replication in S.cerevisiaeEukaryotic origins of DNA replication display a significant inter-species diversity.In higher eukaryotes this diversity reaches a point where origin locations are difficult to identify by homology search (Mechali, 2010).A remarkable exception of this diversity occurs in the yeast S.cerevisiae.In this organism the first functional origins have been identified by screens for DNA elements which confer DNA replication on plasmids (Stinchcomb et al., 1979;Chan & Tye, 1980;Kearsey, 1983).Comparison between these autonomously replicating sequences (ARSs) have shown that they encompass approximately 200bp of DNA and contain perfect or one-base mismatches to the 11 bp ARS consensus sequence (ACS) 5'-WTTAYRTTTW-3' (where W=A/T; Y=C/T; R=A/G).Linker scanning substitutions in several ARSs have determined that the ACS is the sole essential element for DNA replication (Marahrens & Stillman, 1992;
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.001 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.009 | 0.007 |
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".