Think global, act local - how to regulate S phase from individual replication origins

All eukaryotes use similar proteins to licence replication origins but, par adoxically, origin DNA is much less conserved. Specific binding sites for t hese proteins have now been identified on fission yeast and Drosophila chro mosomes, suggesting that the DNA-binding activity of the origin recognition complex has diverged to recruit conserved initiation factors on polymorphi c replication origins. Once formed, competent origins are activated by cycl in- and Dbf4-dependent kinases. The latter have been shown to control S pha se in several organisms but, in contrast to cyclin-dependent kinases, seem regulated at the level of individual origins. Global and local regulations generate specific patterns of DNA replication that help establish epigeneti c chromosome states.