Timing and spacing of ubiquitin-dependent DNA damage bypass

► Tolerance to replication-blocking DNA lesions is essential for genome stability. ► Damage bypass can be accomplished at replication forks or at daughter-strand gaps. ► A major part of damage bypass in eukaryotes is controlled by ubiquitylation of PCNA. ► Ubiquitin-dependent translesion synthesis occurs independently of replication forks. ► Higher eukaryotes also use fork-associated mechanisms for damage bypass.