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Record W4389322750 · doi:10.1101/2023.12.03.569808

Homologous recombination contributes to the repair of acetaldehyde-induced DNA damages

2023· preprint· en· W4389322750 on OpenAlexfundno aff
Kosuke Yamazaki, Kazuto Takayasu, Trinh Thi To Ngo, Ayaka Onuki, Hideya Kawaji, Shunji Oshima, Tomomasa Kanda, Hisao Masai, Hiroyuki Sasanuma

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2023
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCarcinogens and Genotoxicity Assessment
Canadian institutionsnot available
FundersJapan Society for the Promotion of ScienceInstitute of GeneticsTokyo Metropolitan Institute of Medical Science
KeywordsAcetaldehydeRAD51Homologous recombinationDNA repairDNA damageDNAChemistryMutantBiochemistryMolecular biologyBiologyGeneEthanol

Abstract

fetched live from OpenAlex

Abstract Acetaldehyde, a chemical that can cause DNA damage and contribute to cancer, is prevalently present in our environment, e.g., in alcohol, tobacco, and food. Although aldehyde potentially promotes crosslinking reaction among biological substances including DNA, RNA, and proteins, it remains unclear what types of DNA damage are caused by acetaldehyde and how they are repaired. In this study, we examined acetaldehyde sensitivity of DNA damage-deficient cells established from human TK6 cell line. Among the mutants, mismatch repair mutants did not show a hypersensitivity to acetaldehyde, while cells deficient in base and nucleotide excision repair pathways increased its sensitivity. We found a delayed repair and hypersensitivity in homologous recombination (HR)-deficient cells but not in non-homologous end joining-deficient cells after acetaldehyde treatment. By analyzing the formation of acetaldehyde-induced RAD51 foci, which represent HR intermediates, HR-deficient cells, but not NHEJ, exhibits delayed repair of acetaldehyde-induced DNA damages, compared with wild-type . These results suggest that acetaldehyde causes complex DNA damages that requires various types of repair pathways. Interestingly, mutants deficient in TDP1 and TDP2, which are involved in the removal of protein adducts from DNA ends, exhibited hypersensitivity to acetaldehyde. the acetaldehyde sensitivity of the TDP1 -/- /RAD54 -/- double mutant was similar to that of each single mutant. This epistatic relationship between TDP1 and RAD54 suggests that that the removal of protein-DNA adducts generated by acetaldehyde needs to be removed for efficient repair by HR. Our study would help understand the molecular mechanism of genotoxic and mutagenic effects of acetaldehyde.

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)0.0010.000
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 head0.018
GPT teacher head0.249
Teacher spread0.231 · 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
Published2023
Admission routes1
Has abstractyes

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