To maintain genome integrity in eukaryotes, DNA must be duplicated precisely 
once before cell division occurs. A process called replication licensing ensures 
that chromosomes are replicated only once per cell cycle. Its control has been 
uncovered by the discovery of the CDKs (cyclin dependent kinases) as master 
regulators of the cell cycle and the initiator proteins of DNA replication, such 
as the Origin Recognition Complex (ORC), Cdc6/18, Cdt1 and the MCM complex. At 
the end of mitosis, the MCM complex is loaded on to chromatin with the aid of 
ORC, Cdc6/18 and Cdt1, and chromatin becomes licensed for replication. CDKs, 
together with the Cdc7 kinase, trigger the initiation of replication, recruiting 
the DNA replicating enzymes on sites of replication. The activated MCM complex 
appears to play a key role in the DNA unwinding step, acting as a replicating 
helicase and moves along with the replication fork, at the same time bringing 
the origins to the unlicensed state. The cycling of CDK activity in the cell 
cycle separates the two states of replication origins, the licensed state in 
G1-phase and the unlicensed state for the rest of the cell cycle. Only when CDK 
drops at the completion of mitosis, is the restriction on licensing relieved and 
a new round of replication is allowed. Such a CDK-regulated licensing control is 
conserved from yeast to higher eukaryotes, and ensures that DNA replication 
takes place only once in a cycle. Xenopus laevis and mammalian cells have an 
additional system to control licensing. Geminin, whose degradation at the end of 
mitosis is essential for a new round of licensing, has been shown to bind Cdt1 
and negatively regulate it, providing a new insight into the regulation of DNA 
replication in higher eukaryotes.