Figure 1: Replication fork impediments and processing pathways
A: Graphical representation of a co-transcriptional R-loop, formed by nascent DNA becomin bound to the template strand behind the polymerase.
B: Replication pass a polymerase blocking lesion: first, the leading strand polymerase stalls but the replisome continues forming a region of ssDNA ahead of the fork. The polymerase can be restarted either by trans-lesion synthesis or by template switching to use the newly synthesised lagging strand as a template.
C: Initiation of BIR: a stalled replication fork reverses, is resected then invades the template DNA aided by the homologous recombination machinery. Replication can then restart in a migrating D-loop with uncoupled synthesis of the lagging strand, using Pif1 as a helicase to improve processivity.