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Record W4402336198 · doi:10.1101/2024.09.05.611390

Molecular basis for CSB stimulation of the SNM1A DNA repair nuclease

2024· preprint· en· W4402336198 on OpenAlexaff
Rebecca Roddan, William J. Nathan, Afaf H. El‐Sagheer, Tom Brown, J.A. Newman, David M. Wilson, Christopher J. Schofield, Peter J. McHugh

Bibliographic record

VenuebioRxiv (Cold Spring Harbor Laboratory) · 2024
Typepreprint
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsDiscovery Centre
Fundersnot available
KeywordsNucleaseChromatinDNAExonucleaseDNA repairChemistryUbiquitinTranscription (linguistics)Cell biologyBiochemistryBiologyMolecular biologyPolymeraseGene

Abstract

fetched live from OpenAlex

Abstract The Cockayne Syndrome B (CSB, ERCC6 ) protein, interacts with the exonuclease SNM1A during transcription-coupled DNA interstrand (ICL) repair, with CSB facilitating localisation of SNM1A to ICL damage. The functional and mechanistic details of this interaction in DNA repair, however, have not been defined. Here, we demonstrate that CSB enhances SNM1A resection through ICLs and identify a specific interaction between the winged-helix domain of CSB and the nuclease core of SNM1A that is crucial for recruitment and enhancement of nuclease degradation. Biochemical and single-molecule studies on DNA containing site-specific ICLs reveal that CSB increases the affinity of SNM1A to damaged DNA substrates and also alters the substrate conformation to enhance ICL processing by SNM1A. Notably, CSB was observed preferentially as a dimer when colocalised with SNM1A at ICLs, constrasting with its monomeric nature observed during repair initiation in classical transcription-coupled nucleotide excision repair. The combined results provide molecular insights into the basis of a direct contribution of CSB to a DNA repair reaction.

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 score0.003
Threshold uncertainty score0.009

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 integrity0.0000.000
Insufficient payload (model declined to judge)0.0030.001

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 head0.009
GPT teacher head0.223
Teacher spread0.213 · 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

Citations2
Published2024
Admission routes1
Has abstractyes

Explore more

Same venuebioRxiv (Cold Spring Harbor Laboratory)→Same topicDNA Repair Mechanisms→French-language works237,207→