Dealing with Gene-Dosage Imbalance during S Phase

DNA replication perturbs the dosage balance between genes that replicate early during S phase and those that replicate late. If propagated to influence protein content, this dosage imbalance could influence cellular functions. In bacteria, mechanisms have evolved to use this imbalance to tune certain processes with the rate of cell growth. By contrast, eukaryotes buffer this dosage imbalance to ensure gene expression homeostasis also during S phase. Here, we outline classical and more recent studies describing how different organisms deal with this replication-dependent dosage imbalance, and describe recent results linking the eukaryotic buffering mechanism to replication-dependent histone acetylation. Finally, we discuss the possible implications of this buffering mechanism and speculate why it is specific to eukaryote cells.