Sonneville et al. reveal how C. elegans embryos control replication licensing factors to promote efficient DNA duplication while preventing the genome from being copied more than once.
A cell starts preparing to duplicate its DNA before it has finished dividing. Beginning in anaphase, the cell flags replication origins where DNA replication will commence. Licensing factors cooperate to mark replication origins by clamping the Mcm2–7 complex around the DNA. Once a cell has tagged a large number of replication origins, it shuts down licensing before S phase so that each section of DNA will be duplicated only once.
Using live-cell imaging, Sonneville et al. followed the dynamics of licensing factors in C. elegans. The researchers propose that the specific behavior of the proteins makes licensing more efficient. Two of the main licensing factors, the origin recognition complex (ORC) and CDC-6, attach to DNA independently, potentially speeding up replication licensing. And the binding of the Mcm2–7 proteins to DNA encouraged the release of CDC-6 and the ORC, allowing them to move on and mark other origins.
Sonneville et al. also determined how a cell curtails replication licensing to stop double duplication of its DNA: the cell expels CDC-6 and ORC from the nucleus during interphase, a process that required the nuclear export factor XPO-1. Depleting this molecule slowed removal of CDC-6 and ORC components from the nucleus and allowed DNA rereplication.