Genome instability caused by codirectional and head-on encounters. (a) Schematic of a circular chromosome with genes oriented codirectional or head-on to replication fork movement (b) Codirectional encounter between backtracked RNAP and a replication fork. DNA synthesis by the replisome can be reprimed by mRNA or primase-initiated RNA synthesis following the encounter with RNAP. The replisome and RNAP collision creates a gap on the leading strand behind the repriming event (28, 81). Following excision of the repriming RNA, a gap remains in the leading strand that could be converted to a double-strand break during the next round of DNA replication when the gap is encountered by the replisome. (c) RNAP moving head-on toward a replication fork. Head-on encounters between RNAP and the replisome can block fork progression. Although several outcomes can occur, the fork can be restored by evicting RNAP and enabling primosome-dependent fork restart (47,61a). Abbreviation: RNAP, RNA polymerase. Part of this figure is adapted from Reference 18.