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Role of Ku in the DNA damage response activated from telomeres

2013· article· en· W190305305 on OpenAlexaff
Victoria L. Fell, Caroline Schild‐Poulter

Bibliographic record

VenueThe FASEB Journal · 2013
Typearticle
Languageen
FieldMedicine
TopicTelomeres, Telomerase, and Senescence
Canadian institutionsRobarts Clinical TrialsWestern University
Fundersnot available
KeywordsKu70TelomereDNA damageKu80Cell cycleDNA repairCell biologyDownregulation and upregulationBiologyTelomere-binding proteinCell cycle checkpointDNAMolecular biologyApoptosisGeneGeneticsTranscription factorDNA-binding protein

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.001
Threshold uncertainty score0.002

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0010.000

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.

Opus teacher head0.015
GPT teacher head0.248
Teacher spread0.234 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

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".

Quick stats

Citations0
Published2013
Admission routes1
Has abstractyes

Explore more

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