Impact of gcn5-F221A on the growth rate of GCN5 synthetic lethal genes.

We examined 22 gene knockouts with known synthetic lethal interactions to gcn5 null. The gcn5-F221A dominant mutant was expressed at varying levels in the background of a knockout strain and growth rate was measured (Table S2). Three gene knockouts, Δccr4, Δrsc2, and Δrtt109, are highly impacted by the gcn5-F221A mutant and exhibited a more than a 20% reduction in growth rate when the gcn5-F221A mutant was highly expressed, indicating these synthetic lethal pairings are highly dependent on Gcn5p catalytic activity. The majority of the genes show a moderate decrease in growth rate as mutant expression is increased while several showed no growth rate changes. Most of these synthetic lethal interactions are not impacted by catalytic activity, but rather require Gcn5p for a protein-protein or protein-DNA interaction. Ten gene deletions were randomly selected as a control and none exhibit any response (Table S2).