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

التفاصيل البيبلوغرافية
العنوان: CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival
المؤلفون: Minguillón Pedreño, Jordi, Ramírez de Haro, Ma. José, Rovirosa Mulet, Llorenç, Bustamante-Madrid, Pilar, Camps-Fajol, Cristina, de Garibay, Gorka Ruiz, Shimelis, Hermela, Montanuy Escribano, Helena, Pujol, Roser, Hernández Viedma, Gonzalo, Bogliolo, Massimo, Castillo, Pau, Soucy, Penny, Martrat, Griselda, Gómez Moruno, Antonio, Cuadras, Daniel, García, María J, Gayarre, Javier, Lazaro Garcia, Conxi, Benitez, Javier, Couch, Fergus J., Pujana, Miquel Ãngel, Surrallés i Calonge, Jordi
سنة النشر: 2022
المجموعة: Universitat Autònoma de Barcelona: Dipòsit Digital de Documents de la UAB
مصطلحات موضوعية: BRCA2, Breast cancer, CDK5RAP3, DNA repair, Chemoresistance
الوصف: 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.
نوع الوثيقة: article in journal/newspaper
وصف الملف: application/pdf
اللغة: English
تدمد: 20726694
العلاقة: Ministerio de Ciencia e Innovación CB06/07/0023; Ministerio de Ciencia e Innovación RTI2018-098419-B-I00; Agència de Gestió d'Ajuts Universitaris i de Recerca SGR/2017-449; Instituto de Salud Carlos III PI18/01029; Instituto de Salud Carlos III PI21/01306; European Commission 223175; Cancers; Vol. 14 Núm. 2 (1-2 2022), p. 353; https://ddd.uab.cat/record/255156Test; urn:10.3390/cancers14020353; urn:oai:ddd.uab.cat:255156; urn:scopus_id:85123103804; urn:articleid:20726694v14n2p353; urn:pmid:35053516; urn:pmc-uid:8773632; urn:pmcid:PMC8773632; urn:oai:pubmedcentral.nih.gov:8773632; urn:oai:egreta.uab.cat:publications/327d7327-2fa3-442a-beea-dda640df41cc
الإتاحة: https://ddd.uab.cat/record/255156Test
حقوق: open access ; Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original. ; https://creativecommons.org/licenses/by/4.0Test/
رقم الانضمام: edsbas.AA5C9DFC
قاعدة البيانات: BASE
الوصف
تدمد:20726694