ATP hydrolysis-driven structural transitions within the Rad51 and Dmc1 nucleoprotein filaments.

Homologous recombination (HR) is essential for the maintenance of genome stability and for generating genetic diversity during meiosis. The eukaryotic protein Rad51 is member of the Rad51/RecA family of DNA recombinases and is responsible for guiding the DNA pairing reactions that take place in HR during mitosis. Dmc1 is a meiosis-specific paralog of Rad51 and is responsible for the DNA pairing reactions that take place in HR during meiosis. Rad51 and Dmc1 are both ATP-dependent DNA-binding proteins and both form extended helical filaments on ssDNA which are key intermediates in HR. The stability of these nucleoprotein filaments is highly regulated and is also tightly coupled to nucleotide binding and hydrolysis. ATP binding promotes filament assembly whereas the hydrolysis of ATP to ADP reduces filament stability to promote filament disassembly. Here, we present CryoEM structures of the recombinases Rad51 and Dmc1 in the ADP-bound states and provide a detailed structural comparison to the ATP-bound filaments. Our findings yield insights into the structural transitions that take place during the hydrolysis of ATP to ADP and suggest a new model for how these structural changes may be linked to nucleoprotein filament disassembly.