Replication of eukaryotic genomes is limited to once per cell cycle, by a 
two-step mechanism. DNA replication origins are first "licensed" during G1 phase 
by loading of an inactive DNA helicase (Mcm2-7) into pre-replicative complexes 
(pre-RCs). Initiation then occurs during S phase, triggered by cyclin-dependent 
kinases (CDKs), which promote recruitment of proteins required for helicase 
activation and replisome assembly. CDKs and the anaphase promoting 
complex/cyclosome (APC/C) restrict licensing to G1 phase by directly and 
indirectly regulating pre-RC components, including ORC, Cdc6, Cdt1, and Mcm2-7. 
Despite the fundamental importance of licensing regulation, the mechanisms by 
which pre-RC components are regulated differ widely across Eukarya. Here we show 
that even within the genus Saccharomyces, Cdc6 is regulated differently in 
different species. We propose that two factors contribute to the rapid evolution 
of licensing regulation. The first is redundancy: eliminating any single 
pre-RC-regulatory mechanism has very little affect on viability. The second is 
interchangeability: we show that regulatory mechanisms can be swapped between 
pre-RC components without compromising the block to re-replication. These 
experiments provide a framework for understanding the diversity of licensing 
regulation in eukaryotes and provide new tools for manipulating the 
chromosome-replication cycle.