Repositorio de producción científica de la Universidad de Sevilla

The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2′-deoxycytidine lesions

Opened Access The PARP inhibitor Olaparib disrupts base excision repair of 5-aza-2′-deoxycytidine lesions

Citas

buscar en

Estadísticas
Icon
Exportar a
Autor: Orta Vázquez, Manuel Luis
Höglund, Andreas
Calderón Montaño, José Manuel
Domínguez García, Inmaculada
Burgos Morón, Estefanía
Visnes, Torkild
Pastor Carrillo, Nuria María
Ström, Cecilia
López Lázaro, Miguel
Helleday, Thomas
Departamento: Universidad de Sevilla. Departamento de Biología Celular
Fecha: 2014
Publicado en: Nucleic Acids Research, 42, (14), 9108-9120
Tipo de documento: Artículo
Resumen: Decitabine (5-aza-21-deoxycytidine, 5-azadC) is used in the treatment of Myelodysplatic syndrome (MDS) and Acute Myeloid Leukemia (AML). Its mechanism of action is thought to involve reactivation of genes implicated in differentiation and transformation, as well as induction of DNA damage by trapping DNA methyltranferases (DNMT) to DNA. We demonstrate for the first time that base excision repair (BER) rec- ognizes 5-azadC-induced lesions in DNA and medi- ates repair. We find that BER (XRCC1) deficient cells are sensitive to 5-azadC and display an increased amount of DNA single- and double-strand breaks. The XRCC1 protein co-localizes with DNMT1 foci af- ter 5-azadC treatment, suggesting a novel and spe- cific role of XRCC1 in the repair of trapped DNMT1. 5-azadC-induced DNMT foci persist in XRCC1 defec- tive cells, demonstrating a role for XRCC1 in repair of 5-azadC-induced DNA lesions. Poly (ADP-ribose) polymerase (PARP) inhibition prevents XRCC1 relo- cation to DNA damage sites, dis...
[Ver más]
Tamaño: 6.126Mb
Formato: PDF

URI: http://hdl.handle.net/11441/41298

DOI: http://dx.doi.org/10.1093/nar/gku638

Mostrar el registro completo del ítem


Esta obra está bajo una Licencia Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 Internacional

Este registro aparece en las siguientes colecciones