Origins of DNA replication on eukaryotic genomes have been observed to fire 
during S phase in a coordinated manner. Studies in yeast indicate that origin 
firing is affected by several factors, including checkpoint regulators and 
chromatin modifiers. However, it is unclear what the mechanisms orchestrating 
this coordinated process are. Recent studies have identified factors that 
regulate the timing of origin activation, including Rif1 which plays crucial 
roles in the regulation of the replication timing program in yeast as well as in 
higher eukaryotes. In mammalian cells, Rif1 appears to regulate the structures 
of replication timing domains through its ability to organize chromatin loop 
structures. Regulation of chromatin architecture by Rif1 may be linked to other 
chromosome transactions including recombination, repair, or transcription. This 
review summarizes recent progress in the effort to elucidate the regulatory 
mechanisms of replication timing of eukaryotic replicons.