How Rif1 bridles rapid embryonic DNA synthesis: Metazoan genomes are duplicated by the coordinated activation of groups of replication origins at different times during the S phase. However, how this is regulated, especially during early vertebrate development, still needs to be determined.

Behind the Paper in Cell& Molecular Biology Community of Nature PortofolioThe faithful duplication of the genetic material is crucial for the cell. With several thousand active replication origins to ensure this task in vertebrates, the spatial and temporal coordination of the replication program is strictly regulated to avoid that no DNA is left unreplicated upon entry into mitosis. The temporal program of DNA replication is a conserved signature for genomes of multicellular organisms. It has been known that transcribed and euchromatin regions generally replicate early, and heterochromatin replicates late in differentiated cells. This positive correlation between transcription and early replication led to the general assumption that a regulated, temporal replication program does not exist in cell cycles where transcription and the distinction between eu and heterochromatin is absent, like in early, rapid cell cycles during the development of amphibians, fishes or insects. Before the onset of zygotic transcription, which takes place after 12 cell divisions in the model organism Xenopus laevis, cells rely only on maternally supplied factors to quickly increase cell number until the mid-blastula transition when cell cycles slow down, and the S phases lengthen. Our findings here further extend previous studies in early Xenopus and Zebrafish cell cycles and strongly suggest that regulated temporal regulation of DNA replication at the level of large chromatin domains exists before the onset of transcription. How did we come to this conclusion