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Record W4220848529 · doi:10.1073/pnas.2111404119

A DNA repair-independent role for alkyladenine DNA glycosylase in alkylation-induced unfolded protein response

2022· article· en· W4220848529 on OpenAlexaff
Larissa Milano, Clara Forrer Charlier, Rafaela Rafognatto Andreguetti, Thomas C. Cox, Eleanor Healing, Marcos Paulo Machado Thomé, Ruan Elliott, Leona D. Samson, Jean‐Yves Masson, Guido Lenz, João Antônio Pêgas Henriques, Axel Nohturfft, Lisiane B. Meira

Bibliographic record

VenueProceedings of the National Academy of Sciences · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicEndoplasmic Reticulum Stress and Disease
Canadian institutionsUniversité LavalCentre hospitalier universitaire de Québec
FundersMinistério da Ciência, Tecnologia e InovaçãoNational Institute of Environmental Health SciencesConselho Nacional de Desenvolvimento Científico e TecnológicoRoyal Society
KeywordsUnfolded protein responseXBP1DNA glycosylaseDNA damageDNA repairMethyl methanesulfonateDNAEndoplasmic reticulumCellular stress responseBiologyChemistryGeneCell biologyBiochemistryFight-or-flight responseMolecular biology

Abstract

fetched live from OpenAlex

Significance Stress response pathways, such as the DNA damage response and the UPR, are critical in the etiology and treatment of cancer and other chronic diseases. Knowledge of an interplay between ER stress and genome damage repair is emerging, but evidence linking defective DNA repair and impaired ER stress response is lacking. Here, we show that AAG is necessary for UPR activation in response to alkylating agents. AAG-deficient mice and human cancer cells are impaired in alkylation-induced UPR. Strikingly, this defect can be complemented by an AAG variant defective in glycosylase activity. Our studies suggest that AAG has noncanonical functions and identify AAG as a point of convergence for stress response pathways. This knowledge could be explored to improve cancer treatment.

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 score0.005

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 integrity0.0000.001
Insufficient payload (model declined to judge)0.0010.001

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 head0.020
GPT teacher head0.286
Teacher spread0.265 · 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

Citations12
Published2022
Admission routes1
Has abstractyes

Explore more

Same venueProceedings of the National Academy of SciencesSame topicEndoplasmic Reticulum Stress and DiseaseFrench-language works237,207