APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer
| العنوان: | APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer |
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| المؤلفون: | Simak Ali, Frances V. Fuller-Pace, Laki Buluwela, Luca Magnani, Naveenan Navaratnam, Roslin Russell, Carlos Caldas, Jason S. Carroll, Anna Maria Ochocka, Manikandan Periyasamy, Van T. M. Nguyen, Hetal Patel, Ross S. Thomas, Chun-Fui Lai, Wilbert Zwart, Alison Harrod, Balázs Győrffy, Ekaterina Nevedomskaya, Judit Remenyi, R. Charles Coombes |
| المساهمون: | Breast Cancer Now, Cancer Research UK, Caldas, Carlos [0000-0003-3547-1489], Carroll, Jason [0000-0003-3643-0080], Apollo - University of Cambridge Repository |
| المصدر: | Cell Reports Cell Reports, Vol 13, Iss 1, Pp 108-121 (2015) |
| بيانات النشر: | Elsevier BV, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | DNA End-Joining Repair, Transcription, Genetic, Estrogen receptor, Cytidine, DOUBLE-STRAND BREAKS, 0601 Biochemistry and Cell Biology, ACTIVATION, chemistry.chemical_compound, Cytidine deamination, TRANSCRIPTION, RNA, Small Interfering, lcsh:QH301-705.5, GENE-EXPRESSION, Regulation of gene expression, Cytidine deaminase, Base excision repair, Prognosis, Gene Expression Regulation, Neoplastic, Deamination, DNA-REPAIR, APOBEC3B, Female, Trefoil Factor-1, Life Sciences & Biomedicine, Protein Binding, Signal Transduction, Breast Neoplasms, Biology, Article, OVARIAN-CANCER, DEMETHYLATION, General Biochemistry, Genetics and Molecular Biology, MECHANISMS, Minor Histocompatibility Antigens, Cell Line, Tumor, Cytidine Deaminase, Humans, Cell Proliferation, Science & Technology, Binding Sites, Tumor Suppressor Proteins, Estrogen Receptor alpha, Cell Biology, DNA, Survival Analysis, Molecular biology, ALPHA, lcsh:Biology (General), chemistry, 1116 Medical Physiology, Cancer research, Estrogen receptor alpha, DNA Damage |
| الوصف: | Summary Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER) and to repair by non-homologous end-joining (NHEJ) pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action. Graphical Abstract Highlights • APOBEC3B is associated with poor survival in ER+ breast cancer patients • APOBEC3B controls breast cancer cell growth by promoting ER transcriptional activity • APOBEC3B can cause C-to-U mutations at ER target genes, to activate DNA repair • Repair of APOBEC3B-induced lesions allows chromatin remodelling that stimulates gene expression Periyasamy et al. show that APOBEC3B is required for the regulation of gene expression by the estrogen receptor in breast cancer cells. They report APOBEC3B can promote cytidine deamination at gene regulatory regions, with consequent repair providing a mechanism for chromatin remodelling that facilitates gene expression. |
| وصف الملف: | application/pdf |
| تدمد: | 2211-1247 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b663f5091c6a5cc46f7b2d488a399b18 https://doi.org/10.1016/j.celrep.2015.08.066 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....b663f5091c6a5cc46f7b2d488a399b18 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 22111247 |
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