Referencia

Jimeno, S., Camarillo, R., Mejías-Navarro, F., Fernández-Ávila, M.J.,Soria-Bretones, I., Prados-Carvajal, R., Huertas, P., 2018. The Helicase PIF1 Facilitates Resection over Sequences Prone to Forming G4 Structures. Cell Rep. 24 (12), 3262–3273 portada cellreports

Autores

Sonia Jimeno, Rosa Camarillo, Fernando Mejías-Navarro, María Jesús Fernández Ávila, Isabel Soria-Bretones, Rosario Prados-Carvajal, Pablo Huertas.

Resumen

DNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or by homologous recombination (HR. The decision between these two routes of DNA repair is a key point of the DNA damage response (DDR) that is controlled by DNA resection. The core machinery catalyzing the resection process is well established. However, little is known about the additional requirements of DNA resection over DNA structures with high complexity. Here, we found evidence that the human helicase PIF1 has a role in DNA resection, specifically for defined DNA regions, such as those prone to form G-quadruplexes. Indeed, PIF1 is recruited to the site of DNA damage and physically interacts with proteins involved in DNA resection, and its depletion causes DNA damage sensitivity and a reduction of HR efficiency. Moreover, G4 stabilization by itself hampers DNA resection, a phenomenon suppressed by PIF1 overexpression.

Descripción

La resección del ADN es un proceso clave en la respuesta al daño celular. Sin embargo, aunque la maquinaria implicada en dicho proceso está bien caracterizada en eucariotas, aún se desconocen los factores adicionales necesarios para reseccionar a través de estructuras atípicas del ADN, como los cuádruplex de Guaninas o G-cuádruplex. En este artículo, se describe cómo la helicasa PIF1 facilita la resección a través de las secuencias del ADN que tienden a formar estas estructuras de G-cuádruplex permitiendo de este modo el acceso de la maquinaria de resección al daño.

 

 

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REFERENCIA DEL GRUPO INVESTIGADOR

El grupo dirigido por el Dr Pablo Huertas, en el cual se ha desarrollado este trabajo, se centra en el estudio de los mecanismos implicados en la reparación del ADN y cómo afecta la correcta progresión de dichos mecanismos en diversas enfermedades, como el cáncer. Esta labor se lleva a cabo en el Centro Andaluz de Biología Molecular y Medicina Regenerativa (CABIMER) y en la Universidad de Sevilla.

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