Select: Cell Cycle

Re-replicating G2 cells (cyclin B1, red; EdU, green). Image courtesy of E. Julien. An Epigenetic License to Replicate Chromosome replication needs to occur once and only once during the cell cycle to produce daughter cells with accurate genetic content. Licensing of replication origins is one form of DNA synthesis regulation, in which origins are loaded with pre-replication complex (RC) proteins during the end of M phase and throughout G1. Without this licensing event, replication origins cannot be activated. New findings from Tardat et al. identify the methyltransferase PR-Set7—and the histone modification that it catalyzes, methylation of histone H4 lysine 20 (H4K20me1)—as a key regulator of the onset of licensing in mammalian cells. The authors show that PR-Set7 and H4K20me1 levels are cell cycle regulated—both are high during M and G1 phases, dropping in S when synthesis begins—and that proteasomal degradation of PR-Set7 is needed to prevent DNA re-replication. The authors also show that silencing PR-Set7 leads to decreased chromatin loading of pre-RC proteins and reduced origin firing during S phase, whereas targeting PR-Set7 to nonorigin sites on the chromatin is sufficient to induce H4K20me1 and the assembly of pre-RC proteins. Future studies are needed to investigate how H4K20me1 facilitates chromatin loading of pre-RC proteins. M. Tardat et al. (2010). Nat. Cell Biol. Published online October 17, 2010. 10.1038/ncb2113.