DNA facilitates oligomerization and prevents aggregation via DNA networks

Abstract Previous studies have shown that nucleic acids can nucleate protein aggregation in disease-related proteins, but in other cases can act as molecular chaperones that prevent protein aggregation, even under extreme conditions. In this study, we describe the link between these two behaviors through a combination of electron microscopy and aggregation kinetics. We find that two different proteins become soluble under harsh conditions through oligomerization with DNA. These DNA:protein oligomers form “networks,” which increases the speed of oligomerization. The cases of DNA both increasing and preventing protein aggregation are observed to stem from this enhanced oligomerization. This observation raises interesting questions abou the role of nucleic acids in aggre3gate formation in disease states.