Each of our cells must cope with tens of thousands of DNA lesions a day. Depending on the exact nature of these lesions and the cell cycle phase the cells are in, the repair will be carried out by one of the DNA repair pathways. Cells face a special challenge when they encounter a DNA lesion when either performing DNA replication in S phase or while performing DNA repair synthesis (which is the gap-filling step of the DNA repair process). The catalytic site of the replicative DNA polymerases, utilized during the DNA elongation processes, is compact and cannot accommodate most DNA lesions. Consequently, DNA synthesis arrests at most forms of DNA lesions. This is when a polymerase switch is initialized on PCNA, where the replicative DNA polymerase is replaced by translesion polymerases to bypass these lesions. This process is called translesion synthesis (TLS). While TLS polymerase activation is well studied during S phase in replicating cells, almost nothing is known about their function in other cell cycle phases (like G0 and G1) or in non-replicating cells.