The cyclin-dependent kinases (Cdks) have an even bigger role in DNA replication than researchers thought, Thomson et al. reveal. The enzymes not only activate individual replication sites, they also control the large-scale pattern of DNA duplication by turning on clusters of replication forks known as replication factories.

DNA replication sticks to a script. Large sections of the genome duplicate in a particular sequence during S phase. What drives the replication timing program is a mystery. Possible candidates are the Cdks, which spur individual replication origins to start copying. The researchers tested how Cdks contribute using hamster cell nuclei in Xenopus egg extracts, a setup that accelerates DNA duplication while preserving the copying pattern.

Thomson et al. found that inhibiting Cdks slowed or even stopped progression through the timing program. Stimulating Cdk activity had the opposite effect. Those results indicate that Cdks ensure that cells move from stage to stage in the replication program. The researchers then determined how this is achieved. Boosting Cdk activity increased the number of working replication factories, in many cases without changing the number of replication forks within each factory. Overall, the findings suggest that Cdks can advance the replication timing program by enlisting additional replication factories. How Cdks switch the factories on remains to be determined.

et al
J. Cell Biol.