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, they 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 increase 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 about the role of nucleic acids in aggregate formation in disease states.