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

作者：Lopez Saavedra Ana; Gomez Cabello Daniel; Salud Dominguez Sanchez Maria; Mejias Navarro Fernando; Jesus Fernandez Avila Maria; Dinant Christoffel; Isabel Martinez Macias Maria; Bartek Jiri; Huertas Pablo

来源：Nature Communications, 2016, 7(1): 12364.

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/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.

• 出版日期2016-8