Figure 1.

1a structure, inhibition of DNA synthesis, S-phase progression and histone acetylation in vivo by 1a. (A) Structures of 1a (Spd(N¹)-CoA), and the acetylated side chain of a lysine residue within the polypeptide chain of a protein targeted by the acetylating enzyme (R1 and R2 are the main chain elements on both sides of the lysyl residue). (B) [³H]-thymidine incorporation into DNA of H358 cells measured after a 6 hour pulse carried out at intervals 6–12 hrs (12 hr curve), at 18–24 hrs (24 hr curve), or at 42–48 hrs (48 hr curve) after the addition of variable concentrations of 1a, and represented as % of control (untreated) cells. (C) Cell cycle analysis of propidium iodide-stained cells at the indicated times after addition of 50 μM 1a. Percent of cells in G₁, S and G₂ represents the average of two independent profiles. Arrows indicate major effects observed in the G₂ (4N) population. (D) SDS-PAGE/western analysis of histones H3-K9 acetylated, H3-K56 acetylated, H3-K9 methylated and total histone H3, before treatment (“C”, control), or at the indicated times post-addition of 50 μM 1a. Each lane = 60 μg protein.