Adjacent replication origins in Mouse Embryonic Fibroblasts (MEFs) are activated simultaneously, and SMC protein seems to have a vital role in their activation

DNA replication in eukaryotes is a complicated process, due to the large size of the genome, and due to the need for the recruitment of many proteins. Furthermore, the need of the activation of thousands of replication origins is another aspect that adds to the complexity of the replication in higher eukaryotes. However, despite its complexity, the replication efficiency remains very high, making it an interesting issue to research. The initiation of the replication, and the activation of the origins of replication, and whether there is a certain model that they are activated in or whether they are activated spontaneously remain unclear. By using DNA combing, we were able to measure the temporal order of activation of adjacent origins. Using this methodology, we show that adjacent origins of replication in mouse embryonic Fibroblasts (MEFs) are activated mostly simultaneously. On the other hand, in cells replicating under replication stress (both Aph and HU), a majority of the origins are activated non-simultaneously. In addition, in our work we also raise the possibility that the SMC protein has an important role both in response to stress and in controlling the activation of the origins.