Replication initiation is limited to once per cell cycle by oscillating master regulators in both prokaryotes and eukaryotes. (A) Caulobacter cell cycle. The swarmer cell sheds its polar flagellum, and in the presence of low CtrA (red) and high DnaA (purple), DNA replication can initiate in the new stalked cell. (Colored arcs) Presence of the indicated master regulator protein, (curved ellipses) circular chromosome. (B) Generalized eukaryotic cell cycle. The APC is active from the metaphase-to-anaphase transition in late mitosis through most of G1 phase, keeping CDK–cyclin activity low and allowing loading of pre-RC complexes and origin licensing. When S-phase CDK cyclins are activated at the onset of S phase, licensed origins fire simultaneously.