Histone gene dosage phenotypes. (A) Sensitivity of sml1Δ cells to histone overexpression. pMS383 (ARS-CEN-TRP1-GAL-HHT1) and pRS414 (ARS-CEN-TRP1) were transformed into wild-type (PKY090), sml1Δ (PKY2503), and rad53Δ sml1Δ (PKY2703) strains. Cells were grown to log phase and plated onto synthetic glucose media lacking tryptophan (−Trp) or synthetic galactose media lacking tryptophan (Gal − Trp) to induce overexpression of histone H3. Plates were incubated at 30°. (B) asf1Δ cells are sensitive to increased histone gene dosage. Wild-type (PKY090) and asf1Δ (PKY993) cells were transformed with either a 2μ-plasmid containing all four histone genes (+histones, pPK128) or an empty 2μ-plasmid (+vector, yEP351). Transformants were then grown to log phase, and 10-fold serial dilutions were plated onto media lacking leucine (−Leu) and incubated at 30°. (C) asf1Δ cells are sensitive to reduced histone gene dosage. Cells lacking both Asf1 and one of the two gene pairs encoding histones H3 and H4 (HHT1-HHF1) grow slowly. Log-phase cultures of the indicated genotypes were plated onto rich media (YPD) and incubated at 30°. Strains were PKY090 (wild type), PKY408 (hht1-hhf1Δ), PKY993 (asf1Δ), and PKY1027 (asf1Δ hht1-hhf1Δ).