A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection

López-Saavedra, Ana, Gómez-Cabello, Daniel, Domínguez-Sánchez, María, Mejrías-Navarro, Fernando, Fernández-Ávila, Marría Jesús, Dinant, Christoffel, Martínez Macías, María Isabel, Bartek, Jiri and Huertas, Pablo (2016) A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection. Nature Communications, 7 (1). pp. 1-14. ISSN 2041-1723

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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/endjoining 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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Depositing User: Maria Isabel Martinez Macias
Date Deposited: 23 Nov 2017 16:31
Last Modified: 18 Jul 2019 15:00
URI: http://sro.sussex.ac.uk/id/eprint/71531

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