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Record W2903908034 · doi:10.1038/s41467-018-07799-2

BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment

2018· article· en· W2903908034 on OpenAlexfundno aff
Giuseppina D’Alessandro, Donna R. Whelan, Sean Howard, Valerio Vitelli, Xavier Renaudin, Marek Adamowicz, Fabio Iannelli, Corey Winston Jones-Weinert, Mi-Young Lee, Valentina Matti, Wei Ting C. Lee, Michael J. Morten, Ashok R. Venkitaraman, Petr Ćejka, Eli Rothenberg, Fabrizio d’Adda di Fagagna

Bibliographic record

VenueNature Communications · 2018
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsnot available
FundersDuke Cancer InstituteNational Cancer InstituteMedical Research CouncilRegione LombardiaNational Science FoundationAssociazione Italiana per la Ricerca sul CancroNational Institute of General Medical SciencesFondazione TelethonUniversity of OxfordRutgers Cancer Institute of New JerseyInstitute of GeneticsNational Institutes of HealthSchweizerischer Nationalfonds zur Förderung der Wissenschaftlichen ForschungAmerican Cancer SocietyFondazione Cariplo
KeywordsRAD51Genome instabilityDNA damageRNADNA repairBiologyDNARNase PHomologous recombinationCell biologyRNase HMolecular biologyGeneticsGene

Abstract

fetched live from OpenAlex

DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.

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 communication0.0010.000
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 head0.044
GPT teacher head0.324
Teacher spread0.280 · 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

Citations243
Published2018
Admission routes1
Has abstractyes

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Same venueNature CommunicationsSame topicDNA Repair MechanismsFrench-language works237,207