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APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Periyasamy, Manikandan 
Patel, Hetal 
Lai, Chun-Fui 
Nguyen, Van TM 
Nevedomskaya, Ekaterina 

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.

Description

Keywords

Binding Sites, Breast Neoplasms, Cell Line, Tumor, Cell Proliferation, Cytidine, Cytidine Deaminase, DNA, DNA Damage, DNA End-Joining Repair, Deamination, Estrogen Receptor alpha, Female, Gene Expression Regulation, Neoplastic, Humans, Minor Histocompatibility Antigens, Prognosis, Protein Binding, RNA, Small Interfering, Signal Transduction, Survival Analysis, Transcription, Genetic, Trefoil Factor-1, Tumor Suppressor Proteins

Journal Title

Cell Rep

Conference Name

Journal ISSN

2211-1247
2211-1247

Volume Title

13

Publisher

Elsevier BV
Sponsorship
Cancer Research UK (C14303/A17197)
Cancer Research UK (16942)
Cancer Research UK (20411)