The polyamines: putrescine, spermidine and spermine, are ubiquitous polycations which have numerous, unique interactions in eukaryotic cells. Polyamines are essential for cell growth, with the bulk of polyamine expression co-ordinated with the cell cycle. The length, charge, and charge distribution of polyamines permit them to interact with large anionic molecules such as DNA, RNA, and phospholipids. Here, a mechanism is proposed whereby cell cycle expression of polyamines at the start of S phase leads to disruption of transcription and splicing, giving priority to DNA and histone synthesis. Inappropriate initiation of this process in non-viable cells leads to apoptosis and may be an underlying cause of autoimmunity.