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Record W4205488419 · doi:10.3390/cancers14020353

CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival

2022· article· en· W4205488419 on OpenAlexafffund
Jordi Minguillón, Marı́a José Ramı́rez, Llorenç Rovirosa, Pilar Bustamante‐Madrid, Cristina Camps-Fajol, Gorka Ruíz de Garibay, Hermela Shimelis, Helena Montanuy, Roser Pujol, Gonzalo Hernández, Massimo Bogliolo, Pau Castillo Bosch, Penny Soucy, Griselda Martrat, Antonio Gómez, Daniel Cuadras, María J. García, Javier Machín Gayarre, Conxi Lázaro, Javier Benı́tez, Fergus J. Couch, Miguel Ángel Pujana, Jordi Surrallés

Bibliographic record

VenueCancers · 2022
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicDNA Repair Mechanisms
Canadian institutionsUniversité LavalCentre hospitalier universitaire de Québec
FundersNational Cancer InstituteInstituto de Salud Carlos IIICanadian Institutes of Health ResearchMinistero dello Sviluppo EconomicoInstitució Catalana de Recerca i Estudis AvançatsCancer Research UKGovernment of CanadaCentres de Recerca de CatalunyaFondation du cancer du sein du QuébecMinisterio de Ciencia, Innovación y UniversidadesEuropean CommissionBreast Cancer Research FoundationFanconi Anemia Research FundGeneralitat de CatalunyaMinistère du Développement Économique, de l’Innovation et de l’ExportationAgencia Estatal de InvestigaciónGenome CanadaNational Institutes of HealthOvarian Cancer Research Fund
KeywordsGenome instabilityHomologous recombinationDNA repairBreast cancerDNA damageBRCA2 ProteinBiologyCancer researchOvarian cancerDNAGeneticsMutationCancerGermline mutationGene

Abstract

fetched live from OpenAlex

BRCA2 is essential for homologous recombination DNA repair. BRCA2 mutations lead to genome instability and increased risk of breast and ovarian cancer. Similarly, mutations in BRCA2-interacting proteins are also known to modulate sensitivity to DNA damage agents and are established cancer risk factors. Here we identify the tumor suppressor CDK5RAP3 as a novel BRCA2 helical domain-interacting protein. CDK5RAP3 depletion induced DNA damage resistance, homologous recombination and single-strand annealing upregulation, and reduced spontaneous and DNA damage-induced genomic instability, suggesting that CDK5RAP3 negatively regulates double-strand break repair in the S-phase. Consistent with this cellular phenotype, analysis of transcriptomic data revealed an association between low CDK5RAP3 tumor expression and poor survival of breast cancer patients. Finally, we identified common genetic variations in the CDK5RAP3 locus as potentially associated with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. Our results uncover CDK5RAP3 as a critical player in DNA repair and breast cancer outcomes.

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: Observational · Consensus signal: none
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.002
Threshold uncertainty score0.005

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)0.0020.000

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 head0.018
GPT teacher head0.250
Teacher spread0.233 · 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 designObservational
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

Citations5
Published2022
Admission routes2
Has abstractyes

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