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Record W4319029686 · doi:10.1038/s41467-023-36195-8

Antecedent chromatin organization determines cGAS recruitment to ruptured micronuclei

2023· article· en· W4319029686 on OpenAlexafffund
Kate MacDonald, Shirony Nicholson-Puthenveedu, Maha M. Tageldein, Sarika Khasnis, C.H. Arrowsmith, Shane M. Harding

Bibliographic record

VenueNature Communications · 2023
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA modifications and cancer
Canadian institutionsStructural Genomics ConsortiumPrincess Margaret Cancer CentreUniversity Health NetworkUniversity of Toronto
FundersNational Institute of General Medical SciencesCanadian Institutes of Health ResearchNatural Sciences and Engineering Research Council of CanadaRobert H. Lurie Comprehensive Cancer CenterGenentechOntario Genomics InstituteGovernment of CanadaNational Cancer InstituteUniversity of TorontoEuropean Federation of Pharmaceutical Industries and AssociationsMerck KGaANational Institutes of HealthOntario GenomicsGenome CanadaMcGill UniversityPfizerNorthwestern UniversityBayerPrincess Margaret Cancer FoundationBristol-Myers Squibb
KeywordsAntecedent (behavioral psychology)ChromatinMicronucleus testBiologyComputational biologyGeneticsCell biologyMedicineGenePsychology

Abstract

fetched live from OpenAlex

Micronuclei (MN) are cytosolic bodies that sequester acentric fragments or mis-segregated chromosomes from the primary nucleus. Spontaneous rupture of the MN envelope allows recognition by the viral receptor cyclic GMP-AMP synthase (cGAS), initiating interferon signaling downstream of DNA damage. Here, we demonstrate that MN rupture is permissive but not sufficient for cGAS localization. Chromatin characteristics such as histone 3, lysine 79 dimethylation (H3K79me2) are present in the nucleus before DNA damage, retained in ruptured MN, and regulate cGAS recruitment. cGAS is further responsive to dynamic intra-MN processes occurring prior to rupture, including transcription. MN chromatin tethering via the nucleosome acidic patch is necessary for cGAS-dependent interferon signaling. Our data suggest that both damage-antecedent nuclear chromatin status and MN-contained chromatin organizational changes dictate cGAS recruitment and the magnitude of the cGAS-driven interferon cascade. Our work defines MN as integrative signaling hubs for the cellular response to genotoxic stress.

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 distilled prediction

Teacher imitation

Not 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.

metaresearch head score (Codex)0.000
metaresearch head score (Gemma)0.000
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.784
Threshold uncertainty score0.421

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

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 head0.039
GPT teacher head0.341
Teacher spread0.302 · 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 teacher head, 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

Citations53
Published2023
Admission routes2
Has abstractyes

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