Multiple roles of the splicing complex SF3B in DNA end resection and homologous recombination

Publication date: Available online 22 April 2018
Source:DNA Repair
Author(s): Rosario Prados-Carvajal, Ana López-Saavedra, Cristina Cepeda-García, Sonia Jimeno, Pablo Huertas
The appropriate repair of DNA double strand breaks is critical for genome maintenance. Thus, several cellular pathways collaborate to orchestrate a coordinated response. These include the repair of the breaks, which could be achieved by different mechanisms. A key protein involved in the regulation of the repair of broken chromosomes is CtIP. Here, we have found new partners of CtIP involved in the regulation of DNA break repair through affecting DNA end resection. We focus on the splicing complex SF3 B and show that its depletion impairs DNA end resection and hampers homologous recombination. Functionally, SF3 B controls CtIP function at, as least, two levels: by affecting CtIP mRNA levels and controlling CtIP recruitment to DNA breaks, in a way that requires ATM-mediated phosphorylation of SF3B2 at serine 289. Indeed, overexpression of CtIP rescues the resection defect caused by SF3 B downregulation. Strikingly, other SF3 B depletion phenotypes, such as impaired homologous recombination or cellular sensitivity to DNA damaging agents, are independent of CtIP levels, suggesting a more general role of SF3 B in controlling the response to chromosome breaks.



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