The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions
|Author||Burgos Morón, Estefanía
Calderón Montaño, José Manuel
Pastor Carrillo, Nuria María
Ruiz Castizo, Ángel
Domínguez García, Inmaculada
López Lázaro, Miguel
Mateos Cordero, Santiago
Orta Vázquez, Manuel Luis
|Department||Universidad de Sevilla. Departamento de Biología Celular
Universidad de Sevilla. Departamento de Farmacología
|Abstract||The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient ...
The Cockayne Syndrome Protein B (CSB) plays an essential role in Transcription-Coupled Nucleotide Excision Repair (TC-NER) by recruiting repair proteins once transcription is blocked with a DNA lesion. In fact, CSB-deficient cells are unable to recover from transcription-blocking DNA lesions. 5-Aza-2′-deoxycytidine (5-azadC) is a nucleoside analogue that covalently traps DNA methyltransferases (DNMTs) onto DNA. This anticancer drug has a double mechanism of action: it reverts aberrant hypermethylation in tumour-suppressor genes, and it induces DNA damage. We have recently reported that Homologous Recombination and XRCC1/PARP play an important role in the repair of 5-azadC-induced DNA damage. However, the mechanisms involved in the repair of the DNMT adducts induced by azadC remain poorly understood. In this paper, we show for the first time the importance of CSB in the repair of azadC-induced DNA lesions. We propose a model in which CSB initiates a signalling pathway to repair transcription blocks induced by incorporated 5-azadC. Indeed, CSB-deficient cells treated with 5-azadC show a delay in the repair of trapped DNMT1, increased levels of DNA damage and reduced survival.
|Cite||Burgos Morón, E., Calderón Montaño, J.M., Pastor Carrillo, N.M., Höglund, A., Ruiz Castizo, Á., Domínguez García, I.,...,Orta Vázquez, M.L. (2018). The Cockayne syndrome protein B is involved in the repair of 5-AZA-2′-deoxycytidine-induced DNA lesions. Oncotarget, 9 (80), 35069-35084.|