Reading, writing, and repair: the role of ubiquitin and the ubiquitin-like proteins in DNA damage signaling and repair
Bibliographic record
Abstract
Genomic instability is both a hallmark of cancer and a major contributing factor to tumor development. Central to the maintenance of genome stability is the repair of DNA damage, and the most toxic form of DNA damage is the DNA double-strand break. As a consequence the eukaryotic cell harbors an impressive array of protein machinery to detect and repair DNA breaks through the initiation of a multi-branched, highly coordinated signaling cascade. This signaling cascade, known as the DNA damage response (DDR), functions to integrate DNA repair with a host of cellular processes including cell cycle checkpoint activation, transcriptional regulation, and programmed cell death. In eukaryotes, DNA is packaged in chromatin, which provides a mechanism to regulate DNA transactions including DNA repair through an equally impressive array of post-translational modifications to proteins within chromatin, and the DDR machinery itself. Histones, as the major protein component of chromatin, are subject to a host of post-translational modifications including phosphorylation, methylation, and acetylation. More recently, modification of both the histones and DDR machinery by ubiquitin and other ubiquitin-like proteins, such as the small ubiquitin-like modifiers, has been shown to play a central role in coordinating the DDR. In this review, we explore how ubiquitination and sumoylation contribute to the "writing" of key post-translational modifications within chromatin that are in turn "read" by the DDR machinery and chromatin-remodeling factors, which act together to facilitate the efficient detection and repair of DNA damage.
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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 | 0.001 | 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 | 0.001 |
| 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".