DNA and nuclear aggregates of polyamines

Abstract

Polyamines (PAs) are linear polycations that are involved in many biological functions. Putrescine, spermidine and spermine are highly represented in the nucleus of eukaryotic cells and have been the subject of decades of extensive research. Nevertheless, their capability to modulate the structure and functions of DNA has not been fully elucidated. We found that polyamines self-assemble with phosphate ions in the cell nucleus and generate three forms of compounds referred to as Nuclear Aggregates of Polyamines (NAPs), which interact with genomic DNA. In an in vitro setting that mimics the nuclear environment, the assembly of PAs occurs within well-defined ratios, independent of the presence of the DNA template. Strict structural and functional analogies exist between the in vitro NAPs (ivNAPs) and their cellular homologues. Atomic force microscopy showed that ivNAPs, as theoretically predicted, have a cyclic structure, and in the presence of DNA, they form a tube-like arrangement around the double helix. Features of the interaction between ivNAPs and genomic DNA provide evidence for the decisive role of "natural" NAPs in regulating important aspects of DNA physiology, such as conformation, protection and packaging, thus suggesting a new vision of the functions that PAs accomplish in the cell nucleus.