Switch-like Compaction of Poly(ADP-ribose) Upon Cation Binding.

Poly(ADP-ribose) (PAR) is an RNA-like homopolymer that regulates DNA repair, RNA metabolism, and biomolecular condensate formation. Dysregulation of PAR results in cancer and neurodegeneration. Although discovered in 1963, fundamental properties of this therapeutically important polymer remain largely unknown. Biophysical and structural analyses of PAR have been exceptionally challenging due to the dynamic and repetitive nature. Here, we present the first single-molecule biophysical characterization of PAR. We show that PAR is stiffer than DNA and RNA per unit length. Unlike DNA and RNA which undergoes gradual compaction, PAR exhibits an abrupt switch-like bending as a function of salt concentration and by protein binding. Our findings points to unique physical properties of PAR that may drive recognition specificity for its function.