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Record W4233545370 · doi:10.24124/2012/bpgub866

Investigating the Cellular Localization of APE1.

2012· dissertation· en· W4233545370 on OpenAlexaff
Sang Eun Kim

Bibliographic record

Venuenot available
Typedissertation
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicRNA Research and Splicing
Canadian institutionsCanadian HeritageUniversity of Northern British ColumbiaLibrary and Archives Canada
Fundersnot available
KeywordsNuclear localization sequenceBiologyExonucleaseNLSDNA repairPopulationAP siteDNARNADNA-(apurinic or apyrimidinic site) lyaseMolecular biologyCell biologyCytoplasmPolymeraseGeneticsGene

Abstract

fetched live from OpenAlex

Apurinic/apyrimidinic endonuclease 1 (APE1) is a well-known DNA repair enzyme with multiple functions which include redox-activation, 3'-DNA phosphodiesterase, 3'-5' DNA exonuclease, and RNase H activities. Recently the novel function of APE1 in RNA metabolism has been demonstrated. APE1 was shown to possess the ability to cleaving single-stranded RNA as well as abasic RNA. It was also shown to physically interact with proteins involved in RNA metabolism. Previous studies have discovered the altered distribution and expression of APE1 in different cell types including cancer cells. The cytoplasmic distribution of APE1 has been shown to have correlation with aggressive carcinomas and poor prognoses for patients. This has led to an increasing number of studies on the undefined extra-nuclear roles of APE1 and APE1's potential implications in cancer development. In this thesis, I aimed (i) to confirm the importance of nuclear localization signal (NLS) of APE1 at the N-terminus, (ii) to discover the role of single nucleotide change of APE1 human population variants in its sub-cellular distribution, (iii) to assess the cellular localization of APE1 with processing bodies and stress granules under cellular stresses, and (iv) to initiate immune-fluorescence analysis of APE1 in breast cancer tissue. Our results revealed that APE1 indeed has an important NLS of 1-20 amino acids at the N-terminus and APE1 human population variants showed nuclear localizations identical to the wild-type APE1. There was no co-localization of APE1 with PBs and/or SBs implying that APE1 is unlikely to be involved in mRNA processing that is carried out in PBs and SGs. We observed redistribution of the ND20-APE1-GFP upon cellular stresses in HepG2 cells and this phenomenon has highlighted possible degradation of the cytoplasmic APE1 upon cellular stress. This finding is also consistent with previous discovery of the five critical lysine residues that are responsible for ubiquitination and APE1 degradation upon cellular stress. In summary, this

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 score0.002
Threshold uncertainty score0.006

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)0.0020.001

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 head0.013
GPT teacher head0.277
Teacher spread0.263 · 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
Published2012
Admission routes1
Has abstractyes

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