An uncharacterized yeast gene has been shown to encode a polyamine acetyltransferase and named PAA1. The recombinant Paa1 protein readily acetylates various polyamines such as putrescine, spermidine, and spermine. paa1 mutants are viable and grow normally under standard conditions. The mutants are sensitive to hydroxyurea, and they are synthetically temperature-sensitive with a rad53-21 mutation. The mutants also show genetic interactions with components of the transcriptional co-activator complex, SAGA, and partially suppress Spt- phenotypes of two spt mutants. These phenotypes suggest that acetylation of polyamines removes them from chromatin and makes the chromatin more accessible. It is known that spermine, but not acetyl spermine, is a precursor in the pathway for synthesis of coenzyme A in yeast. When Paa1 is overexpressed, leading to a lower level of spermine, cells show a growth dependence on either of two downstream compounds in the coenzyme A pathway, pantothenate or beta-alanine. This demonstrates that spermine and perhaps other polyamines are the in vivo targets of Paa1.