Polyamine--DNA nexus: structural ramifications and biological implications

Abstract

Polyamines at physiological concentration can condense DNA, chromatin and promote B to Z DNA transitions. These properties of polyamines are crucial to the molecular organization and functional control of DNA and thus have very significant implications in the control of cellular functions. The structure of polyamines plays an important role in the binding of DNA and chromatin and it is not merely the charge, but a specific chain length of methylene (-CH2) groups that is required. Acetylation of polyamines seems to be an important mode of regulating polyamine-chromatin interaction. Purified histone acetyltransferase also possesses polyamine acetylation activity, thus histones and polyamine acetylation may occur in tandem to alter the structure/function of the nucleosome thereby regulating DNA replication and transcription. Acetylation as a means to diminish the number of charges on polyamine molecules serves as an ordered mechanism to control DNA replication and transcription in vivo. The results on the involvement of polyamines and their analogs in condensation of DNA and B to Z DNA transition correlate well with the conclusions drawn from experiments designed to observe the in vivo effects of polyamines and their analogs on the growth of prokaryotic and eukaryotic cells. For example, any change in the hydrogen bonding capacity of polyamines leads to a marked reduction in protein synthesis and the growth rate of polyamine depleted cells. A minimal level of polyamines is required for cells to move from G1 through S phase and these amines are directly involved in the DNA synthetic phase of the cell cycle. A nexus between polyamines and nucleic acids appears crucial to the cellular function(s) of polyamines.