The ability of cells to tolerate DNA damage, even at the cost of decreased genomic stability, is as biologically important as their ability to repair such damage. Such tolerance to unexcised lesions encountered during replication is attributed to DNA damage bypass pathways that utilize novel Y family polymerases to allow resumption of the movement of DNA replication forks that stall after encountering damage. Translesion synthesis (TLS) utilizes the error-prone DNA polymerase (Pol) zeta, Pol eta and Pol kappa, which lack 3' to 5' exonuclease activities and synthesize DNA with low fidelity and weak processivity. The combination of these activities allows the TLS Pols to bypass the damaged bases and thereby restore movement of a stalled replication fork. Rad6/Rad18 mediated mono-ubiquitination of PCNA plays an important, albeit incompletely worked out, role in recruiting such polymerases at the damaged sites (Edmunds et al. 2008).