Early replication fragile sites: where replication-transcription collisions cause genetic instability

Although it is known that replication stress causes genetic instability, the underlying mechanisms are not yet fully understood. A new study by Barlow et al (2013) used an elegant genome-wide chromatin immunoprecipitation approach to reveal that DNA lesions induced by replication stress occur predominantly in early replicating and actively transcribed gene clusters. These 'early replication fragile sites' (ERFS) can be the source for rearrangements commonly found in cancer, and represent a new type of fragile site, distinct from common fragile sites (CFS).