title: A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection.
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.
authors: Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.|Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: Ana
authors: A
authors: López-Saavedra
authors: Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: Daniel
authors: D
authors: Gómez-Cabello
authors: Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: María Salud
authors: MS
authors: Domínguez-Sánchez
authors: Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.|Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: Fernando
authors: F
authors: Mejías-Navarro
authors: Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: María Jesús
authors: MJ
authors: Fernández-Ávila
authors: Genome Integrity Unit, Danish Cancer Society Research Centre, Strandboulevarden 49, 2100 Copenhagen, Denmark.
authors: Christoffel
authors: C
authors: Dinant
authors: Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.|Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: María Isabel
authors: MI
authors: Martínez-Macías
authors: Genome Integrity Unit, Danish Cancer Society Research Centre, Strandboulevarden 49, 2100 Copenhagen, Denmark.|Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, 171 76 Stockholm, Sweden.
authors: Jiri
authors: J
authors: Bartek
authors: Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.|Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
authors: Pablo
authors: http://orcid.org/0000-0002-1756-4449
authors: P
authors: Huertas
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002843:Chromatin / Q000378:metabolism; D004249:DNA Damage; D059766:DNA End-Joining Repair; D004706:Endodeoxyribonucleases; D053263:Gene Regulatory Networks; D015894:Genome, Human; D006801:Humans; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D059767:Recombinational DNA Repair
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C527450:CCAR2 protein, human; D002352:Carrier Proteins; D002843:Chromatin; D009687:Nuclear Proteins; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human