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

Autor:	Periyasamy M; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Patel H; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Lai CF; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Nguyen VTM; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Nevedomskaya E; Department of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands., Harrod A; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Russell R; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Remenyi J; Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK., Ochocka AM; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Thomas RS; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Fuller-Pace F; Division of Cancer Research, University of Dundee, Ninewells Hospital and Medical School, Dundee DD1 9SY, UK., Győrffy B; MTA TTK Lendület Cancer Biomarker Research Group, Second Department of Pediatrics, Semmelweis University and MTA-SE Pediatrics and Nephrology Research Group, Budapest 1085, Hungary., Caldas C; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Navaratnam N; MRC Clinical Sciences Centre, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Carroll JS; Cancer Research UK, Cambridge Research Institute, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK., Zwart W; Department of Molecular Pathology, The Netherlands Cancer Institute, 1066 CX Amsterdam, the Netherlands., Coombes RC; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Magnani L; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Buluwela L; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK., Ali S; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, Du Cane Road, London W12 0NN, UK. Electronic address: simak.ali@imperial.ac.uk.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2015 Oct 06; Vol. 13 (1), pp. 108-121. Date of Electronic Publication: 2015 Sep 24.
DOI:	10.1016/j.celrep.2015.08.066
Abstrakt:	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. (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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