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Pàgina inicial > Articles > Articles publicats > CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival |
Data: | 2022 |
Resum: | 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. |
Ajuts: | 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 |
Drets: | 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. |
Llengua: | Anglès |
Document: | Article ; recerca ; Versió publicada |
Matèria: | BRCA2 ; Breast cancer ; CDK5RAP3 ; DNA repair ; Chemoresistance |
Publicat a: | Cancers, Vol. 14 Núm. 2 (1-2 2022) , p. 353, ISSN 2072-6694 |
15 p, 2.5 MB |