Fig. 1.

During S phase, the replisome encounters a number of impediments, which could interfere with its progression and have the potential to endanger the stability of the genome. When faced with such obstacles, in many cases, the cell triggers the S phase checkpoint and stabilizes the replication fork. In the event of replication fork breakdown or “collapse,” replication can restart by recruiting an alternative pathway requiring homology-directed repair (HDR), which could eventually result in loss of genetic and/or epigenetic information. If stalled forks fail to restart, persistent checkpoint activation can lead to apoptosis. As discussed in the text, silencing factors are also recruited to sites of replication stress. Possible roles of heterochromatin proteins at these loci could be in preserving the stability of the replisome or in modulating the cellular response to replication stress via largely unknown mechanism(s). Such events could also serve as an initial signal and potentially trigger the formation of heterochromatin