The proper repair of deleterious DNA lesions such as double strand breaks prevents genomic instability and carcinogenesis. In yeast, the Rad52 protein mediates DSB repair via homologous recombination. In mammalian cells, despite the presence of the RAD52 protein, the tumour suppressor protein BRCA2 acts as the predominant mediator during homologous recombination. For decades, it has been believed that the RAD52 protein played only a back-up role in the repair of DSBs performing an error-prone single strand annealing (SSA). Recent studies have identified several new functions of the RAD52 protein and have drawn attention to its important role in genome maintenance. Here, we show that RAD52 activities are enhanced by interacting with a small and highly acidic protein called DSS1. Binding of DSS1 to RAD52 changes the RAD52 oligomeric conformation, modulates its DNA binding properties, stimulates SSA activity and promotes strand invasion. Our work introduces for the first time RAD52 as another interacting partner of DSS1 and shows that both proteins are important players in the SSA and BIR pathways of DSB repair.

CEITEC Masaryk University 62500 Brno Czech Republic

Department of Biochemistry University of Iowa Carver College of Medicine 51 Newton Road Iowa City IA 52242 USA

Department of Biology Masaryk University 62500 Brno Czech Republic

International Clinical Research Center St Anne's University Hospital in Brno 62500 Brno Czech Republic

National Centre for Biomolecular Research Masaryk University 62500 Brno Czech Republic

NMR Core Facility Carver College of Medicine University of Iowa Iowa City IA 52242 USA

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