Damaged double strand DNA (dsDNA) cannot be successfully used as a template by replicative DNA polymerase delta (POLD) and epsilon (POLE) complexes (Hoege et al. 2002). When the replication complex composed of PCNA, RPA, RFC and POLD or POLE stalls at a DNA damage site, PCNA becomes monoubiquitinated by RAD18 bound to UBE2B (RAD6). POLD or POLE dissociate from monoubiquitinated PCNA, while Y family DNA polymerases - REV1, POLH (DNA polymerase eta), POLK (DNA polymerase kappa) and POLI (DNA polymerase iota) - bind monoubiquitinated PCNA through their ubiquitin binding and PCNA binding motifs, resulting in a polymerase switch and initiation of translesion synthesis (TLS) (Hoege et al. 2002, Friedberg et al. 2005).