Role of Ku in the DNA damage response activated from telomeres
Bibliographic record
Abstract
The Ku heterodimer, composed of two subunits, Ku70 and Ku80, is the main DNA binding component of the non homologous end joining (NHEJ) DNA repair pathway. Intriguingly, Ku is also present at telomeres and is required for telomere protection and regulation, but its role in telomere maintenance is not fully understood. We previously showed that Ku70 S155 is involved in regulation of the DNA damage response leading to apoptosis in response to ionizing radiation (IR). Here we show that expression of Ku70 bearing a phosphomimetic substitution (Ku70 S155D) produces a robust DNA damage response, marked by an upregulation of phospho‐H2AX and ATM activation, even in the absence of any DNA damage treatment. Telomere FISH analysis showed colocalization of γ‐H2AX foci with telomere ends. Cells expressing Ku70 S155D displayed cell cycle arrest, in particular in the G2 phase and upregulation of several factors involved in cell cycle arrest. Conversely, cells expressing Ku70 with a S155 alanine substitution (S155A) showed an increased cell growth rate and downregulation of genes involved in cell cycle checkpoints. This suggests that the phosphorylation status of Ku70 S155 regulates the DNA damage response from telomeres to control cell cycle progression, providing a novel role for Ku as a signaling factor at mammalian telomeres.
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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 | 0.000 |
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 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".