APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer.
Ochocka, Anna Maria
Thomas, Ross S
Coombes, R Charles
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Periyasamy, M., Patel, H., Lai, C., Nguyen, V. T., Nevedomskaya, E., Harrod, A., Russell, R., et al. (2015). APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer.. Cell reports, 13 (1), 108-121. https://doi.org/10.1016/j.celrep.2015.08.066
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.
Cell Line, Tumor, Humans, Breast Neoplasms, DNA Damage, Cytidine Deaminase, Tumor Suppressor Proteins, Estrogen Receptor alpha, RNA, Small Interfering, DNA, Cytidine, Minor Histocompatibility Antigens, Prognosis, Survival Analysis, Signal Transduction, Cell Proliferation, Transcription, Genetic, Gene Expression Regulation, Neoplastic, Binding Sites, Protein Binding, Deamination, Female, DNA End-Joining Repair, Trefoil Factor-1
Cancer Research UK (C14303_do not transfer)
External DOI: https://doi.org/10.1016/j.celrep.2015.08.066
This record's URL: https://www.repository.cam.ac.uk/handle/1810/292240
Attribution 4.0 International
Licence URL: https://creativecommons.org/licenses/by/4.0/