APOBEC3B-Mediated Cytidine Deamination Is Required for Estrogen Receptor Action in Breast Cancer.
Cell Rep
; 13(1): 108-121, 2015 Oct 06.
Article
em En
| MEDLINE
| ID: mdl-26411678
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias da Mama
/
Regulação Neoplásica da Expressão Gênica
/
Citidina
/
Citidina Desaminase
/
Receptor alfa de Estrogênio
/
Reparo do DNA por Junção de Extremidades
Tipo de estudo:
Prognostic_studies
Limite:
Female
/
Humans
Idioma:
En
Revista:
Cell Rep
Ano de publicação:
2015
Tipo de documento:
Article
País de afiliação:
Reino Unido