Mechanisms restricting DNA replication to once per cell cycle: the role of Cdc6p and ORC

In our recent trends in CELL BIOLOGY review in May last year, we surveyed the mechanisms that restrict DNA replication to once per cell cycle. We attempted to highlight the convergence of data from different systems on a single unifying theme: replication-competent chromatin is characterized by the presence of chromatin-bound MCM (minichromosome maintenance) proteins and most likely, although direct evidence was still missing, Cdc6p. These proteins are displaced from chromatin during replication, and the regeneration of replication competence in G2 phase is actively prevented by the presence of a kinase activity. The missing links in the model have been rapidly replaced by hard facts, thus necessitating this update.