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

doi:10.1016/j.celrep.2015.08.066

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 language	English
Pages (from-to)	108-121
Number of pages	14
Journal	Cell Reports
Volume	13
Issue number	1
Early online date	24 Sept 2015
DOIs	https://doi.org/10.1016/j.celrep.2015.08.066
Publication status	Published - 6 Oct 2015

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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

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title = "APOBEC3B-mediated cytidine deamination is required for estrogen receptor action in breast cancer",

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.",

author = "Manikandan Periyasamy and Hetal Patel and Chun-Fui Lai and Nguyen, {Van T. M.} and Ekaterina Nevedomskaya and Alison Harrod and Roslin Russell and Judit Remenyi and Ochocka, {Anna Maria} and Thomas, {Ross S.} and Frances Fuller-Pace and Bal{\'a}zs Gy{\H o}rffy and Carlos Caldas and Naveenan Navaratnam and Carroll, {Jason S.} and Wilbert Zwart and Coombes, {R. Charles} and Luca Magnani and Laki Buluwela and Simak Ali",

year = "2015",

month = oct,

day = "6",

doi = "10.1016/j.celrep.2015.08.066",

language = "English",

volume = "13",

pages = "108--121",

journal = "Cell Reports",

issn = "2211-1247",

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Periyasamy, M, Patel, H, Lai, C-F, Nguyen, VTM, Nevedomskaya, E, Harrod, A, Russell, R, Remenyi, J, Ochocka, AM, Thomas, RS, Fuller-Pace, F, Győrffy, B, Caldas, C, Navaratnam, N, Carroll, JS, Zwart, W, Coombes, RC, Magnani, L, Buluwela, L & Ali, S 2015, 'APOBEC3B-mediated cytidine deamination is required for estrogen receptor action in breast cancer', Cell Reports, vol. 13, no. 1, pp. 108-121. https://doi.org/10.1016/j.celrep.2015.08.066

TY - JOUR

T1 - APOBEC3B-mediated cytidine deamination is required for estrogen receptor action in breast cancer

AU - Periyasamy, Manikandan

AU - Patel, Hetal

AU - Lai, Chun-Fui

AU - Nguyen, Van T. M.

AU - Nevedomskaya, Ekaterina

AU - Harrod, Alison

AU - Russell, Roslin

AU - Remenyi, Judit

AU - Ochocka, Anna Maria

AU - Thomas, Ross S.

AU - Fuller-Pace, Frances

AU - Győrffy, Balázs

AU - Caldas, Carlos

AU - Navaratnam, Naveenan

AU - Carroll, Jason S.

AU - Zwart, Wilbert

AU - Coombes, R. Charles

AU - Magnani, Luca

AU - Buluwela, Laki

AU - Ali, Simak

PY - 2015/10/6

Y1 - 2015/10/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.celrep.2015.08.066

DO - 10.1016/j.celrep.2015.08.066

M3 - Article

C2 - 26411678

SN - 2211-1247

VL - 13

SP - 108

EP - 121

JO - Cell Reports

JF - Cell Reports

IS - 1

ER -

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

Abstract

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