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Nat Commun. 2016 Aug 9;7:12364. doi: 10.1038/ncomms12364.

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

Author information

1
Departamento de Genética, Universidad de Sevilla, 41080 Sevilla, Spain.
2
Department of Regenerative Medicine, Centro Andaluz de Biología Molecular y Medicina Regenerativa, 41092 Sevilla, Spain.
3
Genome Integrity Unit, Danish Cancer Society Research Centre, Strandboulevarden 49, 2100 Copenhagen, Denmark.
4
Department of Medical Biochemistry and Biophysics, Science for Life Laboratory, Karolinska Institute, 171 76 Stockholm, Sweden.

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.

PMID:
27503537
PMCID:
PMC4980490
DOI:
10.1038/ncomms12364
[Indexed for MEDLINE]
Free PMC Article

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