RAD51 discrimination between single- and double-strand DNA: a matter of flexibility and enthalpy.

In selecting ssDNA over dsDNA, the RAD51 DNA strand exchange protein has to overcome the entropy associated with straightening of single-strand DNA upon nucleoprotein filament formation. New work in The EMBO Journal (Paoletti et al, 2020), combined biophysical analysis of the RAD51-ssDNA interaction with mathematical modeling to show that the flexibility of DNA positively correlates with nucleation and extension of the RAD51 nucleoprotein filament and that the entropic penalty associated with restricting ssDNA flexibility is offset by a strong RAD51-RAD51 interaction within the nucleoprotein filament.