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

• Published in: Nature communications Vol. 7; no. 1; p. 12364
• Main Authors: López-Saavedra, Ana, Gómez-Cabello, Daniel, Domínguez-Sánchez, María Salud, Mejías-Navarro, Fernando, Fernández-Ávila, María Jesús, Dinant, Christoffel, Martínez-Macías, María Isabel, Bartek, Jiri, Huertas, Pablo
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 09-08-2016; Nature Publishing Group; Nature Portfolio
• Subjects: 13/106; 14/35; 631/337/1427/2122; 631/337/1427/2190; 631/337/149; Adaptor Proteins, Signal Transducing - metabolism; Carrier Proteins - metabolism; Cell cycle; Cell Line, Tumor; Chromatin - metabolism; DNA Damage; DNA End-Joining Repair; Gene Regulatory Networks; Genome, Human; Genomes; Humanities and Social Sciences; Humans; Medicin och hälsovetenskap; Models, Biological; multidisciplinary; Nuclear Proteins - metabolism; Protein Binding; Proteins; Recombinational DNA Repair; Science; Science (multidisciplinary); Spain
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms12364

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.
A DNA double strand break can be repaired through either the non-homologous end-joining or the homologous recombination pathways. Here the authors conduct a genome-wide screen and identify a role for CCAR2 in pathway choice by regulating DNA end resection by CtIP.