If one were to rank cellular processes of critical importance, duplication of the genome must surely be near the top. Its significance as a fundamental process has prompted studies on specific aspects that have revealed that distinct molecular machines operate during different stages of genome duplication. Other studies show that DNA replication is highly regulated so that the genome is duplicated only once per cell cycle. This cell cycle dependence is the result of separate biochemical mechanisms that control DNA replication by modulating the frequency of replication initiation. However, our understanding of these regulatory processes is incomplete. We also know that DNA replication is strictly coordinated with cell growth, but we do not have an understanding of the genetics or biochemistry of this coordination. Hence, major questions remain unanswered
