The replication licensing system acts to ensure that no section of the
genome is replicated more than once in a single cell cycle. Experimen
ts using Xenopus egg extracts have revealed that the licensing system
consists of two components, named RLF-M and RLF-B. Whereas the functio
n of RLF-B is still unclear, RLF-M has been shown to consist of all si
x members of the MCM/P1 family proteins, which appear to be the struct
ural component of the licensing system. The origin recognition complex
(ORC) and Cdc6/Cdc18 are needed on chromatin before the licensing rea
ction can take place, although they are not themselves components of t
he licensing system. Cell cycle events and cyclin-dependent protein ki
nases (Cdks) also seem to be involved in controlling the licensing sys
tem to ensure once per cell cycle DNA replication. The subject of this
review is to detail our current understanding of the licensing system
and the way that it interacts with other components of the cell cycle
machinery.