Figure 2.

The resolution of R-loops determines the fate of head-on collisions. Different events occur on the two filaments according to R-loop resolution. The hybrid can be resolved by enzymatic cleavage by RNase H1/2 or unwinding by DNA: RNA helicases allowing fork restart (upper panel). If left unresolved, the R-loop triggers the replication stress response (lower panel). Different players are recruited to protect the fork, destabilize the R-loop, cleave or resolve the DNA: RNA hybrid. ssDNA filaments are covered by RPA that in turn recruits the ATR/ATRIP complex and initiates the DNA damage and replication stress response cascade.