Within any genome, there are regions that exhibit higher rates of mitotic recombination than the genomic average as the result of their proximity to hotspots or common fragile sites [8]. These regions typically represent slow-replicating sequences, and agents that generate DNA replication stress often reveal their fragility. These regions are also often associated with non-histone protein complexes that inhibit DNA replication fork progression. This generates DNA replication stress that may lead to an increased frequency of DNA damage due to replication fork collapse [9]–[10]. While conservative repair of this DNA damage would have no genetic consequence, the higher incidence of damage results in a greater chance that an alternative repair pathway will be utilized that does confer a genotypic change.
