The stable propagation of genetic information requires that the entire genome of an organism be faithfully replicated only once in each cell cycle. In eukaryotes, this replication is initiated at hundreds to thousands of replication origins distributed ov ...er the genome, each of which must be prohibited from re-initiating DNA replication within every cell cycle. Initiation of DNA replication occurs by a two-step process. In the first step initiation proteins are assembled onto the replication origin in a step-wise fashion to yield an initiation complex. In the second step the initiation complex is activated by protein kinases, resulting in the establishment of replication forks. This process is tightly regulated such that initiation at a given replication origin occurs only once per cell cycle. In addition, initiation is down regulated in response to agents that damage DNA or that block DNA replication.
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