APOBEC3B-mediated cytidine deamination is required for estrogen receptor action in breast cancer

Manikandan Periyasamy, Hetal Patel, Chun-Fui Lai, Van T. M. Nguyen, Ekaterina Nevedomskaya, Alison Harrod, Roslin Russell, Judit Remenyi, Anna Maria Ochocka, Ross S. Thomas, Frances Fuller-Pace, Balázs Győrffy, Carlos Caldas, Naveenan Navaratnam, Jason S. Carroll, Wilbert Zwart, R. Charles Coombes, Luca Magnani, Laki Buluwela, Simak Ali (Lead / Corresponding author)

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    Abstract

    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.

    Original languageEnglish
    Pages (from-to)108-121
    Number of pages14
    JournalCell Reports
    Volume13
    Issue number1
    Early online date24 Sep 2015
    DOIs
    Publication statusPublished - 6 Oct 2015

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    Cite this

    Periyasamy, M., Patel, H., Lai, C-F., Nguyen, V. T. M., Nevedomskaya, E., Harrod, A., Russell, R., Remenyi, J., Ochocka, A. M., Thomas, R. S., Fuller-Pace, F., Győrffy, B., Caldas, C., Navaratnam, N., Carroll, J. S., Zwart, W., Coombes, R. C., Magnani, L., Buluwela, L., & Ali, S. (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