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

被引：92

作者：

Periyasamy, Manikandan ^{[1
]}

Patel, Hetal ^{[1
]}

Lai, Chun-Fui ^{[1
]}

Nguyen, Van T. M. ^{[1
]}

Nevedomskaya, Ekaterina ^{[2
]}

Harrod, Alison ^{[1
]}

Russell, Roslin ^{[3
]}

Remenyi, Judit ^{[4
]}

Ochocka, Anna Maria ^{[1
]}

Thomas, Ross S. ^{[1
]}

Fuller-Pace, Frances ^{[4
]}

Gyorffy, Balazs ^{[5
,6
]}

Caldas, Carlos ^{[3
]}

Navaratnam, Naveenan ^{[7
]}

Carroll, Jason S. ^{[3
]}

Zwart, Wilbert ^{[2
]}

Coombes, R. Charles ^{[1
]}

Magnani, Luca ^{[1
]}

Buluwela, Laki ^{[1
]}

Ali, Simak ^{[1
]}

机构：

[1] Univ London Imperial Coll Sci Technol & Med, Dept Surg & Canc, London W12 0NN, England

[2] Netherlands Canc Inst, Dept Mol Pathol, NL-1066 CX Amsterdam, Netherlands

[3] Canc Res UK, Cambridge Res Inst, Li Ka Shing Ctr, Cambridge CB2 0RE, England

[4] Univ Dundee, Ninewells Hosp & Med Sch, Div Canc Res, Dundee DD1 9SY, Scotland

[5] Semmelweis Univ, Dept Pediat 2, MTA TTK Lendulet Canc Biomarker Res Grp, H-1085 Budapest, Hungary

[6] MTA SE Pediat & Nephrol Res Grp, H-1085 Budapest, Hungary

[7] Univ London Imperial Coll Sci Technol & Med, MRC, Ctr Clin Sci, London W12 0NN, England

来源：

CELL REPORTS | 2015年 / 13卷 / 01期

关键词：

DOUBLE-STRAND BREAKS; GENE-EXPRESSION; DNA-REPAIR; OVARIAN-CANCER; TRANSCRIPTION; APOBEC3B; ALPHA; ACTIVATION; DEMETHYLATION; MECHANISMS;

D O I：

10.1016/j.celrep.2015.08.066

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Estrogen receptor alpha (ER alpha) 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.

引用

页码：108 / 121

页数：14

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