A genome-wide screening uncovers the role of CCAR2 as an antagonist of DNA end resection
journal contributionposted on 2023-06-09, 09:01 authored by Ana López-Saavedra, Daniel Gómez-Cabello, María Domínguez-Sánchez, Fernando Mejrías-Navarro, Marría Jesús Fernández-Ávila, Christoffel Dinant, María Isabel Martínez Macías, Jiri Bartek, Pablo Huertas
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.
- Published version
PublisherNature Publishing Group
Department affiliated with
- Sussex Centre for Genome Damage Stability Publications
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