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A Role for Np95 in Genome Integrity Maintenance.

2010· article· en· W2295841300 on OpenAlexaff
Helena Mistry

Bibliographic record

VenueThe FASEB Journal · 2010
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicUbiquitin and proteasome pathways
Canadian institutionsUniversity of Toronto
Fundersnot available
KeywordsHeterochromatinDNA damageBiologyHistoneGenome instabilityDNA repairHeterochromatin protein 1Cell biologyMolecular biologyG2-M DNA damage checkpointDNA methylationDNAChromatinCell cycle checkpointCell cycleGeneticsCellGene expressionGene

Abstract

fetched live from OpenAlex

Np95 (also known as Uhrf1) is a proliferation‐associated E3 ubiquitin ligase that participates in maintenance of DNA methylation and histone H3 lysine 9 trimethylation trimeH3K9) associated with heterochromatin. Although cells deficient in Np95 have previously been shown to exhibit greater sensitivity to DNA damaging agents, the role of this protein in the cellular response to DNA damage is unknown. Here we report that Np95 is critical for the maintenance of genome integrity. In the absence or presence of DNA damaging agents, Np95 deficiency leads to an increase in the number of cells with chromosomal instability and elevated levels of γH2AX, a cellular marker that signifies the presence of DNA double strand breaks. Although H2AX status has previously been shown to impact checkpoint activation, Np95 deficient cells exhibit intact checkpoint activation compared to wild‐type cells. Furthermore, DNA damage signalling pathways that activate Chk2 and FancD2 are intact in Np95 deficient cells. Loss of Np95 results in a redistribution of focal trimeH3K9 staining to the nuclear periphery. We observed that (ii) focal staining of heterochromatin protein HP1β but not HP1α dissipates following DNA damage and (ii) this loss of focal HP1β staining is accentuated in Np95 deficient cells. Our findings indicate that maintenance of heterochromatin by Np95 is crucial for genome integrity and protection from DNA damage.

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 score0.004

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 communication0.0010.001
Open science0.0000.001
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 head0.014
GPT teacher head0.249
Teacher spread0.235 · 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
Published2010
Admission routes1
Has abstractyes

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