@article{9bbc8f4f2a824e6e9c2f7477bcb985fd,
title = "CDK5RAP3, a New BRCA2 Partner That Regulates DNA Repair, Is Associated with Breast Cancer Survival",
abstract = "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.",
keywords = "BRCA2, Breast cancer, CDK5RAP3, Chemoresistance, DNA repair",
author = "Jordi Minguill{\'o}n and Ram{\'i}rez, {Mar{\'i}a Jos{\'e}} and Lloren{\c c} Rovirosa and Pilar Bustamante-Madrid and Cristina Camps-Fajol and {De Garibay}, {Gorka Ruiz} and Hermela Shimelis and Helena Montanuy and Roser Pujol and Gonzalo Hernandez and Massimo Bogliolo and Pau Castillo and Penny Soucy and Griselda Martrat and Antonio G{\'o}mez and Daniel Cuadras and Garc{\'i}a, {Mar{\'i}a J.} and Javier Gayarre and Conxi L{\'a}zaro and Javier Ben{\'i}tez and Couch, {Fergus J.} and {Angel Pujana}, Miquel and Jordi Surrall{\'e}s",
note = "Funding Information: Funding: Surrall{\'e}s laboratory is supported by the ICREA Academia programme, Spanish Ministry of Science, Innovation and Universities (projects CB06/07/0023 MCI, UE and RTI2018-098419-B-I00 MCI/AEI/FEDER, UE), European Commission (and P-SPHERE COFUND project), Fanconi Anemia Research Fund Inc. This work was also funded by intramural actions (ACCI-U705/U745-2018 to JS) of CIBERER. CIBERER is an initiative of the Instituto de Salud Carlos III, Spain. M.A.P. laboratory was funded by the Instituto de Salud Carlos III grants PI18/01029 and PI21/01306, Generalitat de Catalunya SGR 2017-449, and CERCA Program to IDIBELL. The CIMBA data management and data analysis were supported by Cancer Research UK grants C12292/A20861 and PPRPGM-Nov20\100002. iCOGS: the European Community{\textquoteright}s Seventh Framework Programme under grant agreement n 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 CA148065 and 1U19 CA148112–the GAME-ON initiative), the Department of Defence (W81XWH-10-1-0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer (CRN-87521), and the Ministry of Economic Development, Innovation and Export Trade (PSR-SIIRI-701), Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. The PERSPECTIVE project was supported by the Government of Canada through Genome Canada and the Canadian Institutes of Health Research, the Ministry of Economy, Science and Innovation through Genome Qu{\'e}bec, and The Quebec Breast Cancer Foundation. Publisher Copyright: {\textcopyright} 2022 by the authors.",
year = "2022",
month = jan,
day = "1",
doi = "10.3390/cancers14020353",
language = "English (US)",
volume = "14",
journal = "Cancers",
issn = "2072-6694",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "2",
}