Molecular Cell
Available online 8 June 2017
In Press, Corrected Proof — Note to users
Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair
Olga M. Mazin a1, 3, Havva Keskin 2, 3, Kritika Hanamshet 1, Francesca Storici 2, Alexander V. Mazin 1, 4, ,
1 Department of Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, USA
2 School of Biological Sciences, Georgia Institute of Technology, Atlanta, GA 30332, USA
Received 3 January 2017, Revised 9 May 2017, Accepted 19 May 2017, Available online 8 June 2017
Published: June 8, 2017
DOI: https://doi.org/10.1016/j.molcel.2017.05.019
Highlights
• Rad52 promotes inverse strand exchange between dsDNA and RNA or ssDNA
• RPA stimulates Rad52-promoted inverse strand exchange with RNA
• Rad52 can use non-resected duplex DNA to promote inverse strand exchange
• Rad52 inverse strand exchange is important for RNA-templated DNA repair in vivo
Summary
RNA can serve as a template for DNA double-strand break repair in yeast cells, and Rad52, a member of the homologous recombination pathway, emerged as an important player in this process. However, the exact mechanism of how Rad52 contributes to RNA-dependent DSB repair remained unknown. Here, we report an unanticipated activity of yeast and human Rad52: inverse strand exchange, in which Rad52 forms a complex with dsDNA and promotes strand exchange with homologous ssRNA or ssDNA . We show that in eukaryotes, inverse strand exchange between homologous dsDNA and RNA is a distinctive activity of Rad52; neither Rad51 recombinase nor the yeast Rad52 paralog Rad59 has this activity. In accord with our in vitro results, our experiments in budding yeast provide evidence that Rad52 inverse strand exchange plays an important role in RNA-templated DSB repair in vivo .
Keywords
RNA-dependent DNA repair; homologous recombination; double-strand DNA repair; DNA strand exchange; Rad51; DNA-RNA pairing; Rad59; Rad52 N-terminal domain; DNA end resection; Sae2
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