Replicating dominos

The choreography of DNA replication has been a mysterious black box. How is replication targeted to different, reproducibly localized DNA domains at the early, middle, and late stages of S phase? Rather than invoking a homunculus, Anje Sporbert, Cristina Cardoso (Max Delbrück Center for Molecular Medicine, Berlin, Germany), and colleagues have come up with a domino model that runs itself once the replication program gets started.

Cardoso's group focused on the dynamics of PCNA, a sliding clamp that aids in DNA polymerase processivity. Recovery of fluorescence after bleaching of PCNA was slow, suggesting that PCNA from within a given replication focus is recycled to load at each new Okazaki fragment.

But the picture over the longer term is very different. Based on pulse labeling of DNA replication and PCNA, bulk PCNA is...