Replication Fork vs Choice of Origin

Source: Courbet et al. 2008. Replication fork movement sets chromatin loop size and origin choice in mammalian cells. 

The stability of the genomes relies on a faithful single round of replication. The ORC has been extensively studied but the question we need to address is the spacial distribution of origins. The authors here show that slowing down the replication fork results in the recruitment of latent origins that are not normally used. The "slow" phenotype was the result of depleted nucleotide pools and addition of A+T to the cell culture restores the "fast" phenotype. Using aphidicolin, a drug which targets DNA pol, the authors established the fact that it is replication fork movement and not nucleotide pool sizes that drives the observed phenomenon.

Now, in a "slow" background, restoring "fastness" by addition of A+T results in two steps: First, 30% of the origins would not fire; second, in the next S phase the pattern mimics that of "fast" cells.