Reference

DOI: 10.1038/ncomms12364naturensp 420

Authors

Ana López-Saavedra, Daniel Gómez-Cabello, María Salud Domínguez-Sánchez, Fernando Mejías-Navarro, María Jesús Fernández-Ávila, Christoffel Dinant, María Isabel Martínez-Macías, Jiri Bartek & Pablo Huertas

Abstract

There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining and homologous recombination. Here we identify and characterize novel factors involved in choosing between these pathways; in this study we took advantage of the SeeSaw Reporter, in which the repair of double-strand breaks by homology-independent or -dependent mechanisms is distinguished by the accumulation of green or red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease-prepared siRNA) library, we isolate genes that control the recombination/end-joining ratio. Here we report that two distinct sets of genes are involved in the control of the balance between NHEJ and HR: those that are required to facilitate recombination and those that favour NHEJ. This last category includes CCAR2/DBC1, which we show inhibits recombination by limiting the initiation and the extent of DNA end resection, thereby acting as an antagonist of CtIP.

Description

Los daños más citotóxicos que se producen en el ADN son las roturas de doble cadena, que se reparan por dos mecanismos principales: unión de extremos no homólogos y recombinación homóloga. Utilizando un sistema que permite distinguir entre ambas vías de reparación, hemos identificado nuevos factores involucrados en la elección del método empleado para reparar. Entre ellos destacamos a CCAR2 y demostramos su papel como inhibidor de la recombinación homóloga, actuando como antagonista de la proteína CtIP.

 

Foto grupo1

 

REFERENCIA DEL GRUPO INVESTIGADOR

El grupo de investigación liderado por el Dr. Pablo Huertas Sánchez, ubicado en el Centro Andaluz de Biología Molecular y Medicina Regenerativa y perteneciente a la Universidad de Sevilla, estudia la regulación de la reparación de los cortes de doble cadena en el ADN. Este estudio se basa en la identificación y caracterización de nuevos factores implicados en la reparación y su relevancia en el desarrollo de enfermedades y su tratamiento.

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