Recent experiments in budding yeast and Xenopus have provided new insi
ghts into the regulation of eukaroytic DNA replication. The multi-subu
nit origin recognition complex plays a key role in initiation, remaini
ng bound at origins of replication during most of the cell cycle. Earl
y in the cell cycle, Cdc6 and the Mcm proteins 'reset' chromatin for a
nother round of DNA replication. Cyclin-dependent kinases appear to pl
ay a dual role, both in activating replication origins and blocking th
e formation of new pre-replicative complexes; thus limiting replicatio
n to once per cell cycle.