Replication-induced DNA damage is a potent source of genome instability; however the affected loci are largely uncharacterized. Using high throughput protein-DNA association and transcriptome assays, Barlow, Faryabi et al. generate a genome-wide map of hydroxyurea-induced DNA damage sites. These sites occur soon after replication initiation (early replication fragile sites, or ERFS), unlike well characterized common fragile sites (CFS). ERFS correlate with high transcription, and can arise from the collision of transcription and replication machineries.
This image illustrates how two powerful engines in opposite orientation can lead to damage, such as when replication and transcription engines cross paths, collide and generate genome instability.