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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 Gyorffy
  • , Carlos Caldas
  • , Naveenan Navaratnam
  • , Jason S. Carroll
  • , Wilbert Zwart
  • , R. Charles Coombes
  • , Luca Magnani
  • , Laki Buluwela
  • , Simak Ali*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

98 Scopus citations

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
DOIs
StatePublished - 6 Oct 2015
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2015 The Authors.

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

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